ABSTRACT: Objective: The current SARS-CoV-2 pandemic poses various challenges for health care workers (HCWs). This may affect their mental health, which is crucial to maintain high quality medical care during a pandemic. Existing evidence suggests that HCWs, especially women, nurses, frontline staff, and those exposed to COVID-19 patients, are at risk for anxiety and depression. However, a comprehensive overview of risk and protective factors considering their mutual influence is lacking. Therefore, this study aimed at exploring HCWs' mental health during the SARS-CoV-2 pandemic in Switzerland, investigating the independent effect of various demographic, work- and COVID-related factors on HCWs' mental health. Methods: In an exploratory, cross-sectional, nation-wide online survey, we assessed demographics, work characteristics, COVID-19 exposure, and anxiety, depression, and burnout in 1,406 HCWs during the beginning of the SARS-CoV-2 pandemic in Switzerland. Network analysis was used to investigate the associations among the included variables. Results: Women (compared to men), nurses (compared to physicians), frontline staff (compared to non-frontline workers), and HCWs exposed to COVID-19 patients (compared to non-exposed) reported more symptoms than their peers. However, these effects were all small. Perceived support by the employer independently predicted anxiety and burnout after adjustment for other risk factors. Conclusion: Our finding that some HCWs had elevated levels of anxiety, depression, and burnout underscores the importance to systematically monitor HCWs' mental health during this ongoing pandemic. Because perceived support and mental health impairments were negatively related, we encourage the implementation of supportive measures for HCWs' well-being during this crisis.