We conducted a serologic survey in public service agencies in New York City, New York, USA, during May–July 2020 to determine prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among first responders. Of 22,647 participants, 22.5% tested positive for SARS-CoV-2–specific antibodies. Seroprevalence for police and firefighters was similar to overall seroprevalence; seroprevalence was highest in correctional staff (39.2%) and emergency medical technicians (38.3%) and lowest in laboratory technicians (10.1%) and medicolegal death investigators (10.8%). Adjusted analyses demonstrated association between seropositivity and exposure to SARS-CoV-2–positive household members (adjusted odds ratio [aOR] 3.52 [95% CI 3.19–3.87]), non-Hispanic Black race or ethnicity (aOR 1.50 [95% CI 1.33–1.68]), and severe obesity (aOR 1.31 [95% CI 1.05–1.65]). Consistent glove use (aOR 1.19 [95% CI 1.06–1.33]) increased likelihood of seropositivity; use of other personal protective equipment had no association. Infection control measures, including vaccination, should be prioritized for frontline workers.

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