BACKGROUND: Health-care workers (HCWs) could be at increased occupational risk for SARS-CoV-2 infection. Information regarding prevalence and risk factors for adverse outcomes in HCWs is scarce in Mexico. Here, we aimed to explore prevalence of SARS-CoV-2, symptoms, and risk factors associated with adverse outcomes in HCWs in Mexico City. METHODS: We explored data collected by the National Epidemiological Surveillance System in Mexico City. All cases underwent real-time RT-PCR test. We explored outcomes related to severe COVID-19 in HCWs and the diagnostic performance of symptoms to detect SARS-CoV-2 infection in HCWs. RESULTS: As of July 5 th, 2020, 35,095 HCWs were tested for SARS-CoV-2 and 11,226 were confirmed (31.9%). Overall, 4,322 were nurses (38.5%), 3,324 physicians (29.6%), 131 dentists (1.16%) and 3,449 laboratory personnel and other HCWs (30.8%). After follow-up, 1,009 HCWs required hospitalization (9.00%), 203 developed severe outcomes (1.81%), and 93 required mechanical-ventilatory support (0.82%). Lethality was recorded in 226 (2.01%) cases. Symptoms associated with SARS-CoV-2 positivity were fever, cough, malaise, shivering, myalgias at evaluation but neither had significant predictive value. We also identified 341 asymptomatic SARS-CoV-2 infections (3.04%). Older HCWs with chronic non-communicable diseases, pregnancy, and severe respiratory symptoms were associated with higher risk for adverse outcomes. Physicians had higher risk for hospitalization and for severe outcomes compared with nurses and other HCWs. CONCLUSIONS: We report a high prevalence of SARS-CoV-2 infection in HCWs in Mexico City. No symptomatology can accurately discern HCWs with SARS-CoV-2 infection. Particular attention should focus on HCWs with risk factors to prevent adverse outcomes and reduce infection risk.