United States securities and exchange commission logo

                          March 17, 2021

       Ankit Mahadevia, M.D.
       President and Chief Executive Officer
       Spero Therapeutics, Inc.
       675 Massachusetts Avenue, 14th Floor
       Cambridge, Massachusetts 02139

                                                        Re: Spero Therapeutics,
Statement on Form S-3
                                                            Filed March 11,
                                                            File No. 333-254170

       Dear Dr. Mahadevia:

              This is to advise you that we have not reviewed and will not
review your registration

               Please refer to Rules 460 and 461 regarding requests for
acceleration. We remind you
       that the company and its management are responsible for the accuracy and
adequacy of their
       disclosures, notwithstanding any review, comments, action or absence of
action by the staff.

                                                        Please contact Alan
Campbell at 202-551-4224 with any questions.


                          Division of Corporation Finance

                          Office of Life Sciences
       cc:                                              Matthew J. Gardella,