As filed with the Securities and Exchange Commission on October 6, 2021January 10, 2023

Registration No. 333-          

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM S-3

REGISTRATION STATEMENT

UNDER

THE SECURITIES ACT OF 1933

DELCATH SYSTEMS, INC.

(Exact Name Of Registrant As Specified In Its Charter)

1633 Broadway, Suite 22C

New York, New York 10019

(212) 489-2100

(Address, including zip code, and telephone number, including area code, of registrant’s principal executive offices)

Gerard Michel

Chief Executive Officer

Delcath Systems, Inc.

1633 Broadway, Suite 22C

New York, New York 10019

(212) 489-2100

(Name, address, including zip code, and telephone number, including area code, of agent for service)

Copy to:

Veronica Montagna, Esq.Ryan S. Sansom

McCarter & English,Nicolas H.R. Dumont

Cooley LLP

100 Mulberry500 Boylston Street Four Gateway Center

Newark, New Jersey 07102Boston, Massachusetts 02116

(973)(617) 639-7948937-2300

Approximate date of commencement of proposed sale to the publicpublic: : From time to time after the effective date of this registration statement as determined by the selling securityholders.

If the only securities being registered on this Form are being offered pursuant to dividend or interest reinvestment plans, please check the following box.  ☐

If any of the securities being registered on this Form are to be offered on a delayed or continuous basis pursuant to Rule 415 under the Securities Act of 1933, other than securities offered only in connection with dividend or interest reinvestment plans, check the following box.  ☒

If this Form is filed to register additional securities for an offering pursuant to Rule 462(b) under the Securities Act, please check the following box and list the Securities Act registration number of the earlier effective registration statement for the same offering.  ☐

If this Form is a post-effective amendment filed pursuant to Rule 462(c) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering.  ☐

If this Form is a registration statement pursuant to General Instruction I.D. or a post-effective amendment thereto that shall become effective upon filing with the Commission pursuant to Rule 462(e) under the Securities Act, check the following box.  ☐

If this Form is a post-effective amendment to a registration statement filed pursuant to General Instruction I.D. filed to register additional securities or additional classes of securities pursuant to Rule 413(b) under the Securities Act, check the following box.  ☐

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act. ☐

The information in this prospectus is not complete and may be changed. AThe Selling Stockholders may not sell these securities or accept an offer to buy these securities until the registration statement relating to these securities has been filed with the Securities and Exchange Commission. These securities may not be sold until the registration statementCommission is effective. This prospectus is not an offer to sell these securities, and we areit is not soliciting offers to buy these securities in any state or other jurisdiction where thesuch offer or sale is not permitted.

SUBJECT TO COMPLETION, PRELIMINARY PROSPECTUS DATED OCTOBER 6, 2021JANUARY 10, 2023

Up to 638,1992,140,931 Shares of Common Stock Offered by the Selling Stockholders

This prospectus relates to the offer and resale, from time to time, by the selling stockholders named under the heading “Selling Stockholders” in this prospectus, or their assigns (the “Selling Stockholders”), of up to an aggregate of 638,1992,140,931 shares of our common stock, par value $0.01 per share (“Common Stock”), consisting of (a) up to 237,614 shares of Common Stock that may be issued to Selling Stockholders upon the conversion of up to an aggregate of 2,376.14 shares of our Series E Convertible PreferredCompany’s Common Stock, par value $0.01 per share (the “Series E Preferred“Common Stock”), at a conversion price of $1,198 per share, following an election by such Selling Stockholders to convert the principal amount of, and all interest accruing under, 8% senior secured promissory notes issued by us to such Selling Stockholders (the principal of which is $2 million and accrued interest of up to $846,667 which as of October 5, 2021 is $344,556) into shares of Series E Preferred Stock, (b) up to an aggregate of 378,172 shares of Common Stock that may be issued to a Selling Stockholder, consistingconsist of (i) 250,4171,448,889 shares of Common Stock that may be issued to such Selling Stockholder upon the conversion of up to $3 million principal amount of a loan made to us by such Selling Stockholder (the “Loan”“Shares”) and (ii) 127,755 shares of Common Stock that may be issued to such Selling Stockholder upon the exercise of a warrant for 127,755 shares of our Common Stock issued to such Selling Stockholder in connection with the Loan at an exercise price of $0.01 per share (the “Warrant”), and (c) 22,413 shares of Common Stock held by the Selling Stockholders alland (ii) 692,042 shares of Common Stock (the “Warrant Shares” and together with the Shares, the “Securities”) issuable upon the exercise of pre-funded warrants (the “Warrants”) held by the Selling Stockholders. We are registering the offer and sale of the Common Stock held by the Selling Stockholders to satisfy the registration rights they were granted pursuant to a registration rights agreement entered into on December 7, 2022 in connection with the securities purchase agreement as described in greater detail underof even date thereof. While we will not receive any proceeds from the heading “The Offering” in this prospectus.sale of the Common Stock by the Selling Stockholders, we will receive proceeds from the exercise of any Warrants for cash.

Our registration of shares of Common Stock covered by this prospectus does not mean that the Selling Stockholders will offer or sell any such shares. The Selling Stockholders may sell shares of Common Stock covered by this prospectus in a number of different ways and at varying prices. For additional information on the possible methods of sale that may be used by the Selling Stockholders, you should refer to the section of this prospectus entitled “Plan of Distribution.” The Selling Stockholders may, individually but not severally, be deemed to be an “underwriter” within the meaning of the Securities Act of 1933, as amended (the “Securities Act”), of the shares of Common Stock that they are offering pursuant to this prospectus. The Selling Stockholders will bear all commissions and discounts, if any, attributable to their respective sales of Common Stock hereunder. We will bear all costs, expenses and fees in connection with the registration of the Common Stock. We will not be paying any underwriting discounts or commissions in this offering.

We will not receive any of the proceeds from the shares of Common Stock sold by the Selling Stockholders hereunder. However, assuming (i) the conversion of all of the Series E Preferred Stock following an election to convert the principal amount and all accrued interest under the 8% senior secured promissory notes into such shares, (ii) the conversion of the entire convertible portion of the Loan and (iii) the exercise of the Warrant, we will receive, upon issuance of the Common Stock to the Selling Stockholders $1,278 upon exercise of the Warrant, the outstanding principal amount of the Loan will be reduced by $3 million and the 8% senior secured promissory notes will no longer be outstanding. See “The Offering” and “Use of Proceeds” for more details.

A prospectus supplement may add, update, or change information contained in this prospectus. You should carefully read this prospectus, any applicable prospectus supplement, and the information incorporated by reference in this prospectus and any applicable prospectus supplement before you make your investment decision.

Our Common Stock is traded on The NASDAQNasdaq Capital Market under the symbol “DCTH.” On October 4, 2021,January 9, 2023, the closing price for our Common Stock, as reported on The NASDAQNasdaq Capital Market, was $9.58$3.51 per share. Our principal executive offices are located at 1633 Broadway, Suite 22C, New York, New York 10019.

Investing in our Common Stockthese securities involves a high degree of risk. You should read carefully the risks and uncertainties that are described in (i) thecertain risks. See “Risk Factors” section beginning on page 125 of this prospectus, (ii) theprospectus. See also “Risk Factors” section of any applicable prospectus supplement or amendment, and (iii) underin the “Risk Factors” or similar headings in our periodic reports and other documents filed with the Securities and Exchange Commission (the “SEC”) that are incorporated by reference intoin this prospectus.prospectus for a discussion of the factors you should carefully consider before deciding to purchase these securities.

Neither the SEC nor any state securities commission has approved or disapproved of these securities or determined if this prospectus is truthful or complete. Any representation to the contrary is a criminal offense.

The date of this prospectus is                 , 2021.2023

TABLE OF CONTENTS

i

ABOUT THIS PROSPECTUS

This prospectus relates to the offer and resale, from time to time, by the selling stockholders named under the heading “Selling Stockholders” in this prospectus, or their assigns (the “Selling Stockholders”), of up to an aggregate of 638,199 shares of our common stock, par value $0.01 per share (“Common Stock”), consisting of (a) up to 237,614 shares of Common Stock that may be issued to Selling Stockholders upon the conversion of up to an aggregate of 2,376.14 shares of our Series E Convertible Preferred Stock, par value $0.01 per share (the “Series E Preferred Stock”), at a conversion price of $1,198 per share, following an election by such Selling Stockholders to convert the principal amount of, and all interest accruing under, 8% senior secured promissory notes issued by us to such Selling Stockholders (the principal of which is $2 million, and the accrued interest on which as of October 5, 2021 is $344,556) into shares of Series E Preferred Stock, (b) up to an aggregate of 378,172 shares of Common Stock that may be issued to a Selling Stockholder, consisting of (i) 250,417 shares of Common Stock that may be issued to such Selling Stockholder upon the conversion of up to $3 million principal amount of a loan made to us by such Selling Stockholder (the “Loan”) and (ii) 127,755 shares of Common Stock that may be issued to Such Selling Stockholder upon the exercise of a warrant for 127,755 shares of our Common Stock issued to such Selling Stockholder in connection with the Loan at an exercise price of $0.01 per share (the “Warrant”), and (c) 22,413 shares of Common Stock held by Selling Stockholders, all as described in greater detail under the heading “The Offering” in this prospectus.

We will not receive any of the proceeds from the shares of Common Stock sold by the Selling Stockholders hereunder. However, assuming (i) the conversion of all of the Series E Preferred Stock following an election to convert the principal amount and all accrued interest under the 8% senior secured promissory notes into such shares, (ii) the conversion of the entire convertible portion of the Loan and (iii) the exercise of the Warrant, we will receive, upon issuance of the Common Stock to the Selling Stockholders $1,278 upon exercise of the Warrant, the outstanding principal amount of the Loan will be reduced by $3 million and the 8% senior secured promissory notes will be no longer be outstanding. See “The Offering” and “Use of Proceeds” for more details.

This prospectus is part of a registration statement on Form S-3, thatwhich we have filed with the Securities and Exchange Commission or the SEC,(the “SEC”) using a shelf“shelf” registration process. Under this shelf registration statement,process, the Selling Stockholders may sell Common Stock from time to time sell the Common Stock described in this prospectus in one or more offerings or otherwise as described in this prospectus. This prospectus omits someunder “Plan of the information contained in the registration statement, and reference is made to the full registration statement for further information with regard to us, the Selling Stockholders and the securities being offered by the Selling Stockholders.Distribution.”

This prospectus provides you with a description of our Common Stock as well as other information you should know before investing in our Common Stock. Eachmay be supplemented from time the Selling Stockholders offer and sell our Common Stock hereby, we will provideto time by one or more prospectus supplements or amendments that will contain specific information about the terms of that specific offering of our Common Stock and the specific manner in which it may be offered. Thesupplements. Such prospectus supplement or amendmentsupplements may also add, to, update or change any of the information contained in this prospectus. ToIf there is any inconsistency between the extent that any statement we makeinformation in a prospectus supplement or amendment is inconsistent with statements made in this prospectus, the statements made in this prospectus will be deemed modified or superseded by those made in the prospectus supplement or amendment. You should read both this prospectus and the applicable prospectus supplement, or amendmentyou must rely on the information in the prospectus supplement. You should carefully read both this prospectus and any applicable prospectus supplement together with the additional information described under the headings “Where You Can Find More Information” and Incorporation of Certain Information by Reference” before making an investment decision. This prospectus may not be used to sell our Common Stock unless it is accompanied by a prospectus supplement, or this prospectus is otherwise updated by documents incorporated by reference.

This prospectus contains summaries of certain provisions contained in some of the documents described herein, but reference is made to the actual documents for complete information. All of the summaries are qualified in their entirety by the actual documents. Copies of some of the documents referred to herein have been filed or will be filed or incorporated by reference as exhibits to the registration statement of which this prospectus forms a

RISK FACTORS

An investmentInvesting in shares of our Common Stock involves a high degree of risk. PriorBefore deciding whether to making a decision about investinginvest in shares of our Common Stock, you should consider carefully the specific risk factorsrisks and uncertainties discussed in this section and under the sections entitled “titled Risk Factors” contained in our most recent Annual Report on Form 10-K for the year ended December 31, 2020,and in our most recent Quarterly Report on Form 10-Q, as filed with the SEC on March 31, 2021, which are incorporatedwell as any amendments thereto reflected in this prospectus by reference in their entirety. Additional risk factors that you should carefully consider may be included in our subsequent filings with the SEC, including awhich are incorporated by reference into this prospectus supplement or amendment hereto relating to an offering of our Common Stock by us or the Selling Stockholders. The risks and uncertainties describedin their entirety, together with other information in this prospectus, any applicable prospectus supplement or amendment, and the documents incorporated by reference, hereinany prospectus supplement and any free writing prospectus that we may authorize. These risks and uncertainties are not the only risks and uncertainties we face. Additional risks and uncertainties not presently known to us, or that we currently view as immaterial, may also impair our business. If any of the risks or uncertainties described in this prospectus,our SEC filings or any applicable prospectus supplement or amendment, or the documents incorporated by reference hereinadditional risks and uncertainties actually occur, our business, financial condition, results of operations and cash flow could be materially and adversely affected. In that case, the trading price of our Common Stock could decline perhaps significantly, and you might lose partall or allpart of your investment. Please also read carefully the section titled “Cautionary Note Regarding Forward-Looking Statements.”

The market price of our Common Stock has been, and may continue to be volatile and fluctuate significantly, which could result in substantial losses for investors.

The trading price of our Common Stock has been, and we expect it to continue to be, volatile. The price at which our Common Stock trades depends upon a number of factors, including historical and anticipated operating results, our financial situation, announcements of technological innovations or new products by us or our competitors, our ability or inability to raise the additional capital needed and the terms on which it may be raised, and general market and economic conditions. Some of these factors are beyond our control. Broad market fluctuations may lower the market price of our Common Stock and affect the volume of trading, regardless of our financial condition, results of operations, business or prospects. Among the factors that may cause the market price of our Common Stock to fluctuate are the risks described elsewhere in this “Risk Factors” section and other factors, including:

In addition, the stock markets and the market for pharmaceutical companies in particular, may experience a loss of investor confidence. Such loss of investor confidence may result in extreme price and volume fluctuations in our Common Stock that are unrelated or disproportionate to the operating performance of our business, financial condition or results of operations. These broad market and industry factors may materially harm the market price of our Common Stock and expose the Company to securities class action litigation. Such litigation, even if unsuccessful, could be costly to defend and divert management’s attention and resources, which could further materially harm our financial condition and results of operations.

Sales of a substantial number of shares of our Common Stock in the public market, or the perception that such sales may occur, could adversely affect the market price of our Common Stock and could impair our ability to raise additional equity capital.

Sales of a substantial number of shares of our Common Stock in the public market, or the perception that such sales may occur, could cause the market price of our Common Stock to decline and could impair our ability to raise capital through the sale of additional equity securities. We cannot predict the effect that future sales of shares of our Common Stock or other equity-related securities would have on the market price of our Common Stock.

CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS

This prospectus, and the documents incorporated by reference herein, contain, or will contain, “forward-looking statements” within the meaning of Section 27A of the Private Securities Litigation ReformAct and Section 21E of the Exchange Act of 1995.1934, as amended (the “Exchange Act”). Forward-looking statements can be identified by words such as “intends,” “believes,” “anticipates,” “indicates,” “plans,” “expects,” “suggests,” “may,” “would,” “should,” “potential,” “designed to,” “will,” “ongoing,” “estimate,” “forecast,” “predict,” “could,” and similar references, although not all forward-looking statements contain these words. Forward-looking statements are neither historical facts nor assurances of future performance. These statements are based only on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, projections, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Risks that could cause actual results to vary from expected results expressed in our forward-looking statements include, but are not limited to:

Forward-looking statements speak only as of the date the statements are made. Except as required under the federal securities laws and rules and regulations of the SEC, we undertake no obligation to update or revise forward-looking statements to reflect actual results, changes in assumptions or changes in other factors affecting forward-looking information. We caution you not to unduly rely on the forward-looking statements when evaluating the information presented herein.

USE OF PROCEEDS

We will not receive any of the proceeds from the shares of Common Stock sold by the Selling Stockholders hereunder. However, assuming (i) the conversion of all of the Series E Preferred Stock following an election to convert the principal amount and all accrued interest under the 8% senior secured promissory notes into such shares, (ii) the conversion of the entire convertible portion of the Loan and (iii)

We may receive proceeds from the exercise of the Warrant, we will receive, upon issuanceWarrants to the extent the Warrants are exercised. We can make no assurances that any of the Common StockWarrants will be exercised, or if exercised, the quantity that will be exercised or the period in which such Warrants will be exercised.

We intend to use the Selling Stockholders $1,278 uponnet proceeds from any exercise of the Warrant (which will be usedWarrants for working capital purposes), the outstanding principal amount of the Loan will be reduced by $3 million and the 8% senior secured promissory notes will be no longer be outstanding. We have agreed to pay all costs, expenses and fees relating to the registration of the shares of Common Stock covered by this prospectus.general corporate purposes.

SELLING STOCKHOLDERS

The Common Stock being offered by the Selling Stockholders or eachare those previously issued to the Selling Stockholders, and those issuable to the Selling Stockholders, upon exercise of their donees, pledgees, assignees, transferees or other successors-in-interest,the Warrants. For additional information regarding the issuances of those shares of Common Stock and warrants, see “Summary—Private Placement” above. We are offeringregistering the Common Stock in order to permit the Selling Stockholders to offer the shares for resale from time to time, up to an aggregatetime.

The table below lists the Selling Stockholders and other information regarding the beneficial ownership of 638,199 sharesthe Common Stock by each of Common Stock.the Selling Stockholders. The sharessecond column lists the number of Common Stock coveredbeneficially owned by each selling stockholder, based on its ownership of the Common Stock and the Warrants, as of December 22, 2022, assuming exercise of the Warrants held by the Selling Stockholders on that date, without regard to any limitations on exercises.

The third column lists the Common Stock being offered by this prospectus represent allby the sharesSelling Stockholders.

In accordance with the terms of a registration rights agreement with the Selling Stockholders, this prospectus generally covers the resale of the sum of (i) the number of Common Stock that have been or may be issued to the Selling Stockholders in connection with the transactions described under the heading “The Offering” on page 11 of this prospectus. The following table sets forth certain information with respect to beneficial ownership of our Common Stock as of October 5, 2021 by the Selling Stockholders, as determined in accordance with Rule 13d-3 of the Exchange Act of 1934, as amended (the “Exchange Act”), prior to this offeringPrivate Placement and after this offering. This information has been obtained from the Selling Stockholders or in Schedules 13G or 13D and other public documents filed with the SEC.

The number of(ii) all shares of Common Stock beneficially owned after this offeringissuable upon exercise of the Warrants issued in the Private Placement.The fourth column assumes the sale of all of the Common Stockshares offered by the Selling Stockholders pursuant to this prospectus. However, because

In accordance with the terms of a registration rights agreement with the Selling Stockholders, we are required to use commercially reasonable efforts to keep this registration statement continuously effective under the Securities Act until the date that all the registrable securities covered by this registration statement (i) have been sold, hereunder or pursuant to Rule 144, or (ii) may be sold without volume or manner-of-sale restrictions pursuant to Rule 144 and without the requirement for us to be in compliance with the current public information requirement under Rule 144.

Under the terms of the Warrants, a selling stockholder may not exercise the Warrants to the extent such exercise would cause such selling stockholder, together with its affiliates and attribution parties, to beneficially own a number of Common Stock which would exceed 9.99% of our then outstanding Common Stock following such exercise, excluding for purposes of such determination Common Stock issuable upon exercise of the Warrants which have not been exercised. The number of shares in the second column does not reflect this

limitation. The Selling Stockholders may sell none,all, some or all of the shares of Common Stock covered by this prospectus from time to time, or in another permitted manner, we cannot assure you as to the actual number of shares of Common Stock that will be sold by the Selling Stockholders or that will be held by the Selling Stockholders after completion of any sales. We do not know how long the Selling Stockholder will hold the shares of Common Stock covered by this prospectus before selling them. Information concerning the Selling Stockholders may change from time to time and changed information will be presented in a supplement to this prospectus if and when necessary and required. However, the Selling Stockholders may sell or transfer all or a portionnone of their shares of Common Stock covered byin this prospectus pursuant to any available exemption from the registration requirementsoffering. See “Plan of the Securities Act.

SELLING STOCKHOLDER TABLEDistribution.”

Relationship with Selling Stockholders

On April 8, 2020, we entered into a Board Appointment Agreement, dated as of April 8, 2020, with Rosalind Opportunities Fund I L.P. and Rosalind Maser Fund L.P. (“Rosalind”), pursuant to which Steven Salamon and Gil Aharon, who are principals of Rosalind, have been appointed as directors of the Company’s board of Directors. Certain shares of Common Stock registered for resale hereunder are also held by Roger G. Stoll,Gerard Michel, who is the Chairman of the Board of Directors of the Company and John Purpura, who serves as the Chief OperatingExecutive Officer of the Company. Except as a result

Other than this relationship with Rosalind and Gerard Michel, none of the term loan transaction with Avenue Capital described herein under the heading “Description of the Transactions,” Avenue CapitalSelling Stockholders has not held any position or office with us or any of our predecessors or affiliates within the last three years and has not had a material relationship with us or any of our predecessors or affiliates within the past three years.years, other than as a result of the ownership of our shares of Common Stock or other securities.

PLAN OF DISTRIBUTION

We are registering the shares of Common Stock issued,Each Selling Stockholder, or issuable upon the conversion of Series E Preferred Stock, to the Selling Stockholders to permit the resale of those shares of Common Stock by the holders of the shares of Common Stock from time to time after the date of this prospectus. We will not receive any of the proceeds from the sale by the Selling Stockholders, of the sharessecurities and any of Common Stock. We will bear all feestheir pledgees, assignees and expenses incident to our obligation to register the shares of Common Stock.

The Selling Stockholderssuccessors-in-interest may, sell all or a portion of the share of Common Stock beneficially owned by them and offered hereby from time to time, directlysell any or through oneall of their securities covered hereby on the principal trading market or more underwriters, broker-dealersany other stock exchange, market or agents. If the Shares are sold through underwriters or broker-dealers, the Selling Stockholders will be responsible for underwriting discounts or commissions or agent’s commissions. The shares of Common Stock may be sold on any national securities exchange or quotation servicetrading facility on which the securities may be listed or quoted at the time of sale, in the over-the-counter marketare traded or in transactions otherwise than on these exchanges or systems or in the over-the-counter market and in one or more transactions at fixed prices, at prevailing market prices at the time of the sale, at varying prices determined at the time of sale, or at negotiated prices.private transactions. These sales may be effected in transactions, which may involve crossesat fixed or block transactions. Thenegotiated prices. A Selling StockholdersStockholder may use any one or more of the following methods when selling shares of Common Stock:securities:

The Selling StockholdersStockholder may also may resell all or a portion of the shares of Common Stock in open market transactions in reliance uponsell securities under Rule 144 under the Securities Act, as permitted by that rule, or Section 4(1)any other exemption from registration under the Securities Act, if available, rather than under this prospectus, provided that they meet the criteria and conform to the requirements of those provisions.prospectus.

Broker-dealers engaged by the Selling StockholdersStockholder may arrange for other broker-dealersbrokers dealers to participate in sales. If the Selling Stockholders effects such transactions by selling shares of Common Stock to or through underwriters, broker-dealers or agents, such underwriters, broker-dealers or agentsBroker-dealers may receive commissions in the form ofor discounts concessions or commissions from the Selling Stockholders or commissions from purchasers of the shares of Common Stock for whom they may act(or, if any broker dealer acts as agent or to whom they may sell as principal. Such commissions will befor the purchaser of securities, from the purchaser) in amounts to be negotiated, but, except as set forth in a supplementsupplements to this prospectus,Prospectus, in the case of an agency transaction will not be in excess of a customary brokerage commission in compliance with FINRA Rule 5110.2121.

In connection with salesthe sale of the shares of Common Stock,securities or interests therein, the Selling StockholdersStockholder may enter into hedging transactions with broker-dealers or other financial institutions, which may in turn engage in short sales of the

We willare required to pay certain fees and expenses incurred by usthat we incur incident to the registration of the shares of Common Stock hereunder.securities. We have agreed to indemnify the Selling Stockholders against certain losses, claims, damages and liabilities, including liabilities under the Securities Act.

UnderWe agreed to keep this prospectus effective continuously effective under the Securities Act until the date that all the resale securities laws of some states,being offered by the shares of Common StockSelling Stockholders (i) have been sold pursuant to this registration statement or pursuant to Rule 144, or (ii) may be sold without volume or manner-of-sale restrictions pursuant to Rule 144 and without the requirement for us to be in such statescompliance with the current public information requirement under Rule 144. The resale securities will be sold only through registered or licensed brokers or dealers.dealers if required under applicable state securities laws. In addition, in somecertain states, the sharesresale securities covered hereby may not be sold unless such sharesthey have been registered or qualified for sale in suchthe applicable state or an exemption from the registration or qualification requirement is available and is complied with.

LEGAL MATTERS

The validity of the shares of Common Stock to be offered for resale by the Selling Stockholder under this prospectus will be passed upon for us by McCarter & English,Cooley LLP, Newark, New Jersey.Boston, Massachusetts.

EXPERTS

The consolidated financial statements as of December 31, 20202021 and 20192020 and for each of the two years in the period ended December 31, 20202021 incorporated by reference in this prospectus have been so incorporated in reliance on the report of Marcum, LLP, an independent registered public accounting firm, incorporated herein by reference, given on the authority of said firm as experts in auditing and accounting.

WHERE YOU CAN FIND MORE INFORMATION AND

This prospectus is part of the registration statement on Form S-3 we filed with the SEC under the Securities Act and does not contain all the information set forth in the registration statement. Whenever a reference is made in this prospectus to any of our contracts, agreements or other documents, the reference may not be complete and you should refer to the exhibits that are a part of the registration statement or the exhibits to the reports or other documents incorporated by reference into this prospectus for a copy of such contract, agreement or other document. Because we are subject to the information and reporting requirements of the Exchange Act, we file annual, quarterly and current reports, proxy statements and other information with the SEC. Our SEC filings are available to the public over the Internet at the SEC’s website at http://www.sec.gov.

You may also access our SEC filings at our website www.delcath.com. Our website and the information contained on, or that can be accessed through, our website will not be deemed to be incorporated by reference in, and are not considered part of, this prospectus. You should not rely on our website or any such information in making your decision whether to purchase our securities.

INCORPORATION OF CERTAIN INFORMATION BY REFERENCE

The SEC allows us to incorporate by reference into this prospectus the information contained in other documents we file with the SEC, which means that we can disclose important information to you by referring you to those documents. Any statement contained in any document incorporated or deemed to be incorporated by reference herein shall be deemed to be modified or superseded, for purposes of this prospectus, to the extent that a statement contained in or omitted from this prospectus, or in any other subsequently filed document that also is or is deemed to be incorporated by reference herein, modifies or supersedes such statement. Any such statement so modified or superseded shall not be deemed, except as so modified or superseded, to constitute a part of this prospectus. We incorporate by reference the documents listed below which have been filed by us:

All documents we file with the SEC pursuant to Sections 13(a), 13(c), 14 or 15(d) of the Exchange Act, except as to any portion of any report or documents that is not deemed filed under such provisions, (1) on or after the date of filing of the registration statement containing this prospectus and prior to the effectiveness of the registration statement and (2) on or after the date of this prospectus until the earlier of the date on which all of the securities registered hereunder have been sold or the registration statement of which this prospectus is a part has been withdrawn, shall be deemed incorporated by reference in this prospectus and to be a part of this prospectus from

Up to 638,1992,140,931 Shares of

Common Stock Offered by the Selling Stockholders

PROSPECTUS

, 20212023

We have not authorized any dealer, salesperson or other person to give any information or represent anything not contained in this prospectus. You must not rely on any unauthorized information. If anyone provides you with different or inconsistent information, you should not rely on it. This prospectus does not offer to sell any securities in any jurisdiction where it is unlawful. Neither the delivery of this prospectus, nor any sale made hereunder, shall create any implication that the information in this prospectus is correct after the date hereof.

PART II

INFORMATION NOT REQUIRED IN PROSPECTUS

Item 14. Other Expenses of Issuance and Distribution.

The following table sets forth various expenses being borne by the Company in connection with the sale and distribution of the securities being registered. All of the amounts shown are estimates except for the Securities and Exchange Commission Registration Fee.

Item 15. Indemnification of Directors and Officers.

The Company is incorporated under the laws of the State of Delaware. Section 102(b)(7) of Delaware’s General Corporation Law (the “DGCL”) allows a corporation to provide in its certificate of incorporation that a director of the corporation will not be personally liable to the corporation or its stockholders for monetary damages for breach of fiduciary duty as a director, except where the director breached the duty of loyalty, failed to act in good faith, engaged in intentional misconduct or knowingly violated a law, authorized the payment of a dividend or approved a stock repurchase in violation of Delaware corporate law or obtained an improper personal benefit. Our amended and restated certificate of incorporation provides for this limitation of liability.

Section 145 of the DGCL, or Section 145, provides that a Delaware corporation may indemnify any person who was, is or is threatened to be made, party to any threatened, pending or completed action, suit or proceeding, whether civil, criminal, administrative or investigative (other than an action by or in the right of such corporation), by reason of the fact that such person is or was an officer, director, employee or agent of such corporation or is or was serving at the request of such corporation as a director, officer, employee or agent of another corporation or enterprise. The indemnity may include expenses (including attorneys’ fees), judgments, fines and amounts paid in settlement actually and reasonably incurred by such person in connection with such action, suit or proceeding, provided such person acted in good faith and in a manner he reasonably believed to be in or not opposed to the corporation’s best interests and, with respect to any criminal action or proceeding, had no reasonable cause to believe that his or her conduct was illegal. A Delaware corporation may indemnify any persons who are, were or are a party to any threatened, pending or completed action or suit by or in the right of the corporation by reason of the fact that such person is or was a director, officer, employee or agent of another corporation or enterprise. The indemnity may include expenses (including attorneys’ fees) actually and reasonably incurred by such person in connection with the defense or settlement of such action or suit, provided such person acted in good faith and in a manner he reasonably believed to be in or not opposed to the corporation’s best interests, provided that no indemnification is permitted without judicial approval if the officer, director, employee or agent is adjudged to be liable to the corporation. Where an officer or director is successful on the merits or otherwise in the defense of any action referred to above, the corporation must indemnify him against the expenses which such officer or director has actually and reasonably incurred.

Section 145 further authorizes a corporation to purchase and maintain insurance on behalf of any person who is or was a director, officer, employee or agent of the corporation or is or was serving at the request of the corporation as a director, officer, employee or agent of another corporation or enterprise, against any liability asserted against him and incurred by him in any such capacity, or arising out of his or her status as such, whether or not the corporation would otherwise have the power to indemnify him under Section 145.

Article SEVENTH of the Company’s amended and restated certificate of incorporation provides that no person serving as a director of the Company shall be personally liable to the Company or its stockholders for

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breach of his or her fiduciary duty as a director, except where the director breached his duty of loyalty, failed to act in good faith, engaged in intentional misconduct or a knowing violation of law, authorized the payment of a dividend or approved a stock repurchase in violation of the DGCL or obtained an improper personal benefit.

Article EIGHTH of the Company’s amended and restated certificate of incorporation requires the Company to indemnify any person who may be indemnified by a Delaware corporation pursuant to Section 145 of the DGCL in each situation where the Company is permitted to indemnify such persons.

We have entered into indemnification agreements with our executive officers and directors pursuant to which we have agreed to indemnify such persons against all expenses and liabilities incurred or paid by such person in connection with any proceeding arising from the fact that such person is or was an officer or director of our company, and to advance expenses as incurred by or on behalf of such person in connection therewith.

The indemnification rights set forth above shall not be exclusive of any other right which an indemnified person may have or hereafter acquire under any statute, provision of our certificate of incorporation, our bylaws, agreement, vote of stockholders or disinterested directors or otherwise.

In addition, we maintain standard policies of insurance that provide coverage (1) to our directors and officers against loss rising from claims made by reason of breach of duty or other wrongful act and (2) to us with respect to indemnification payments that we may make to such directors and officers.

A list of exhibits filed with this registration statement on Form S-3 is set forth on the Exhibit Index and is incorporated herein by reference.

The Registrant hereby undertakes:

(a)

(1) To file, during any period in which offers or sales are being made, a post-effective amendment to this Registration Statement:

(i) To include any prospectus required by section 10(a)(3) of the Securities Act of 1933;

(ii) To reflect in the prospectus any facts or events arising after the effective date of the Registration Statement (or the most recent post-effective amendment thereof) which, individually or in the aggregate, represent a fundamental change in the information set forth in the Registration Statement. Notwithstanding the foregoing, any increase or decrease in volume of securities offered (if the total dollar value of securities offered would not exceed that which was registered) and any deviation from the low or high end of the estimated maximum offering range may be reflected in the form of prospectus filed with the Commission pursuant to Rule 424(b) if, in the aggregate, the changes in volume and price represent no more than 20% change in the maximum aggregate offering price set forth in the “Calculation of Registration Fee” table in the effective Registration Statement.

(iii) To include any material information with respect to the plan of distribution not previously disclosed in the Registration Statement or any material change to such information in the Registration Statement;

provided, however, that paragraphs a(i), a(ii) and a(iii) do not apply if the information required to be included in a post-effective amendment by those paragraphs is contained in reports filed with or furnished to the Commission by the registrant pursuant to Section 13 or 15(d) of the Exchange Act that are incorporated by reference in the registration statement.

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(2) That, for the purpose of determining any liability under the Securities Act of 1933, each such post-effective amendment shall be deemed to be a new registration statement relating to the securities offered

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SIGNATURES

Pursuant to the requirements of the Securities Act of 1933, the registrant certifies that it has reasonable grounds to believe that it meets all of the requirements for filing on Form S-3 and has duly caused this registration statement to be signed on its behalf by the undersigned, thereunto duly authorized, in New York, New York, on October 6, 2021.January 10, 2023.

POWER OF ATTORNEY

KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutesWe, the undersigned officers and appointsdirectors of Delcath Systems, Inc. hereby severally constitute and appoint Gerard Michel as attorney-in-fact,our true and lawful attorney with full power of substitution, in any and all capacities, to sign for us and in our names in the capacities indicated below the Registration Statement on Form S-3 filed herewith and any and all amendments (including post-effective amendments) to said Registration Statement, and post-effective amendments to thisany registration statement filed pursuant to Rule 462 under the Securities Act of 1933, as amended, in connection with said Registration Statement, and to file or cause to be filed the same, with all exhibits thereto and other documents in connection therewith, with the Securities and Exchange Commission, and generally to do all such things in our name and on our behalf in our capacities as officers and directors to enable Delcath Systems, Inc. to comply with the provisions of the Securities Act of 1933, as amended, and all requirements of the Securities and Exchange Commission, hereby ratifying and confirming all that said attorney-in-fact,attorney, or his substitute or substitutes, mayshall do or cause to be done by virtue thereof.hereof.

Pursuant to the requirements of the Securities Act of 1933, this registration statement has been signed by the following persons in the capacities and on the dates indicated.

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