Exhibit 32.1

Certification of Principal Executive Officer Pursuant to 18 U.S.C. Section 1350,

As Adopted Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002

I, Alexandra MacLean, M.D., Chief Executive Officer of Avenue Therapeutics, Inc. (the “Company”), in compliance with 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002, hereby certify that, to my knowledge, the Company’s Quarterly Report on Form 10-Q for the period ended March 31, 2023 (the “Report”) filed with the Securities and Exchange Commission:

● Fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934; and

● The information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of the Company.

/s/ Alexandra MacLean, M.D.

Alexandra MacLean, M.D.

Chief Executive Officer

(Principal Executive Officer)

May 12, 2023