Spero Therapeutics, Inc.

675 Massachusetts Avenue, 14th Floor

Cambridge, Massachusetts 02139

March 20, 2024

VIA EDGAR

United States Securities and Exchange Commission

Division of Corporation Finance

100 F Street, N.E.

Washington, D.C. 20549

Attention: Cindy Polynice

RE: Spero Therapeutics, Inc.

Registration Statement on Form S-3 File No. 333-277998

Request for Acceleration of Effectiveness

Ladies and Gentlemen:

In accordance with Rule 461 promulgated under the Securities Act of 1933, as amended, Spero Therapeutics, Inc. (the “Company”) hereby requests acceleration of the effective date of the Registration Statement on Form S-3 (File No. 333-277998) (the “Registration Statement”), so that it may become effective at 4:00 p.m., Washington, D.C. time on March 22, 2024 or as soon as possible thereafter.

The Company hereby authorizes Matthew J. Gardella, Esq. of Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C. to orally modify or withdraw this request for acceleration.

The Company respectfully requests that it be notified of such effectiveness by a telephone call to Mr. Gardella at (617) 348-1735 and that such effectiveness also be confirmed in writing. Any questions regarding this request may be addressed to Mr. Gardella.

Very truly yours,

SPERO THERAPEUTICS, INC.

/s/ Esther Rajavelu

Esther Rajavelu

Chief Financial Officer, Chief Business Officer and Treasurer

cc: Spero Therapeutics, Inc.

Satyavrat Shukla, President and Chief Executive Officer

Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.

Matthew J. Gardella, Esq.

Matthew Tikonoff, Esq.

Lewis J. Geffen, Esq.