BackgroundDuring the initial COVID-19 outbreak, organizational changes were required to ensure adequate staffing in healthcare facilities. The extent to which organizational changes impacted the mental wellbeing of healthcare workers (HCWs) remains unexplored. Here we analyzed the association between three work-related stressors (reported access to protective equipment, change in job functions, and patient prioritization decision-making) and mental health outcomes (depression symptoms, psychological distress, suicidal thoughts, and fear of infection) in a large sample of Spanish HCWs during the initial COVID-19 outbreak. MethodsWe conducted a cross-sectional study including HCWs from three regions of Spain between April 24th and June 22nd, 2020. An online survey measured sociodemographic characteristics, work-related stressors, fear of infection, and mental health outcomes (depression [PHQ-9], psychological distress [GHQ-12], death wishes [C-SSRS]). We conducted mixed-effects regression models to adjust all associations for relevant individual- and region-level sources of confounding. ResultsWe recruited 2,370 HCWs. Twenty-seven percent screened positive for depression and 74% for psychological distress. Seven percent reported death wishes. Respondents were more afraid of infecting their loved ones than of getting infected themselves. All work-related stressors were associated with depression symptoms and psychological distress in adjusted models. LimitationsNon-probabilistic sampling, potential reverse causation. ConclusionsModifiable work-related stressors are associated with worse mental health among HCWs. Our results suggest that workplace prevention strategies for HCWs should provide sufficient protective equipment, minimize changes in job functions, favor the implementation of criteria for patient triage and on-call bioethics committees, and facilitate access to stepped-care, evidence-based mental health treatment.