The purpose of this study was to explore the role of moral distress on physician burnout during COVID-19. Physicians in the US were interviewed between February and March 2021; 479 responded to our survey. Results indicated that moral distress was a key mediator in explaining the relationship between perceived organizational support, medical specialization, emotional labor, and coping on burnout. There was no support for increased burnout among female physicians, and contracting COVID-19 likewise did not play a role in burnout. Our findings suggest that physician burnout can be mitigated by increasing perceived organizational support; likewise, physicians who engaged in deep emotional labor and problem-focused coping tended to fare better when it came to feelings of moral distress and subsequent burnout.