In light of the current coronavirus disease 2019 (COVID-19) pandemic and potential future infectious disease outbreaks, a comprehensive understanding of the negative effects of epidemics and pandemics on healthcare workers’ mental health could inform appropriate support interventions. Thus, we aimed to synthesize and quantify the psychological and psychosomatic symptoms among frontline medical staff. We searched four databases up to March 19, 2020 and additional literature, with daily search alerts set up until October 26, 2020. Studies reporting psychological and/or psychosomatic symptoms of healthcare workers caring for patients with severe acute respiratory syndrome, H1N1, Ebola, Middle East respiratory syndrome, or COVID-19 were eligible for inclusion. Two reviewers independently conducted the search, study selection, quality appraisal, data extraction, and synthesis and involved a third reviewer in case of disagreement. We used random effects modeling to estimate the overall prevalence rates of psychological/psychosomatic symptoms and the <i>I</i><sup>2</sup> statistic. We included 86 studies, reporting data from 75,991 participants. Frontline staff showed a wide range of symptoms, including concern about transmitting the virus to the family (60.39%, 95% CI 42.53–76.96), perceived stress (56.77%, 95% CI 34.21–77.95), concerns about own health (45.97%, 95% CI 31.08–61.23), sleeping difficulties (39.88%, 95% CI 27.70–52.72), burnout (31.81%, 95% CI 13.32–53.89), symptoms of depression (25.72%, 95% CI 18.34–33.86), symptoms of anxiety (25.36%, 95% CI 17.90–33.64), symptoms of posttraumatic stress disorder (24.51%, 95% CI 18.16–31.46), mental health issues (23.11%, 95% CI 15.98–31.10), and symptoms of somatization (14.68%, 95% CI 10.67–19.18). We found consistent evidence for the pervasive and profound impact of large-scale outbreaks on the mental health of frontline healthcare workers. As the COVID-19 crisis continues to unfold, guaranteeing easy access to support structures for the entire healthcare workforce is vitally important.