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We isolated a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BA.2 variant from a person with coronavirus disease 2019 recrudescence after nirmatrelvir/ritonavir treatment. Antiviral sensitivity and neutralizing antibody testing were performed with both parental SARS-CoV-2 and multiple variants of concern. We found that neither nirmatrelvir resistance nor absence of neutralizing immunity was a likely cause of the recrudescence., Competing Interests: Potential conflicts of interest. A. F. C. has received contract payments from Nurix Therapeutics and has options in Covicept Therapeutics. D. M. S. has served as a consultant for Bayer Healthcare, Kiadis Pharmaceuticals, and Signant Health, and has equity stake in Vx Biosciences, Model Medicines, Linear Therapies, and FluxErgy. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)