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Background In early 2020, the COVID-19 pandemic paralyzed the world and exposed the fragility of health systems in the face of mass illness. Health professionals became protagonists, fulfilling their mission at the risk of physical and mental illness. The study aimed to evaluate absenteeism indirectly related to SARS-CoV-2 infection in a large population of health care professionals. Methods An observational longitudinal repeated measures study was performed, including workers linked to 40 public university hospitals in Brazil. All causes of absenteeism were analyzed, focusing on those not directly attributed to COVID-19. Results for the same population were compared over two equivalent time intervals: prepandemic and during the pandemic. Findings A total of 32,691 workers were included in the study, with health professionals comprising 82.5% of the sample. Comparison of the periods before and during the pandemic showed a 26.6% reduction in work absence for all causes, except for COVID-19 and mental health-related absence. Concerning work absence related to mental health, the odds ratio was 39.0% higher during the pandemic. At the onset of the pandemic, there was an increase in absenteeism (all causes), followed by a progressive reduction until the end of the observation period. Interpretation Work absence related to mental illness among health care professionals increased during the COVID-19 pandemic, highlighting the need for health care managers to prioritize and implement support strategies to minimize absenteeism.