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While the global COVID-19 pandemic has been widely acknowledged to affect the mental health of health care workers (HCWs), attention to measures that protect those on the front lines of health outbreak response has been limited. In this cross-sectional study, we examine workplace contextual factors associated with how psychological distress was experienced in a South African setting where a severe first wave was being experienced with the objective of identifying factors that can protect against HCWs experiencing negative impacts. Consistent with mounting literature on mental health effects, we found a high degree of psychological distress (57.4% above the General Health Questionnaire cut-off value) and a strong association between perceived risks associated with the presence of COVID-19 in the healthcare workplace and psychological distress (adjusted OR = 2.35, p < 0.01). Our research indicates that both training (adjusted OR 0.41, 95% CI 0.21–0.81) and the reported presence of supportive workplace relationships (adjusted OR 0.52, 95% CI 0.27–0.97) were associated with positive outcomes. This evidence that workplace resilience can be reinforced to better prepare for the onset of similar outbreaks in the future suggests that pursuit of further research into specific interventions to improve resilience is well merited.