Objective: To evaluate the efficacy of a wellness leadership intervention for improving the empathy, burnout, and physiological stress of medical faculty leaders. Participants and Methods: Participants were 49 medical faculty leaders (80% physicians, 20% basic scientists; 67% female). The 6-week course was evaluated with a 15-week longitudinal waitlist-control quasi-experiment from September 1, 2021, through December 20, 2021 (during the COVID-19 pandemic). We analyzed 3 pretest-posttest-posttest and 6 weekly survey measurements of affective empathy and burnout, and mean=85 (SD=31) aggregated daily resting heart rates per participant, using 2-level hierarchical linear modeling. Results: The course found a preventive effect for leaders’ burnout escalation. As the control group awaited the course, their empathy decreased (coefficientTime=−1.27; P=.02) and their resting heart rates increased an average of 1.4 beats/min (coefficientTime=0.18; P