BACKGROUND: Mental health professionals experiencing work-related stress may experience burn out, leading to a negative impact on their organization and patients. AIM: The aim of this study was to examine the effects of yoga classes on work-related stress, stress adaptation, and autonomic nerve activity among mental health professionals. METHODS: A randomized controlled trial was used, which compared the outcomes between the experimental (e.g., yoga program) and the control groups (e.g., no yoga exercise) for 12 weeks. Work-related stress and stress adaptation were assessed before and after the program. Heart rate variability (HRV) was measured at baseline, midpoint through the weekly yoga classes (6 weeks), and postintervention (after 12 weeks of yoga classes). RESULTS: The results showed that the mental health professionals in the yoga group experienced a significant reduction in work-related stress (t = -6.225, p < .001), and a significant enhancement of stress adaptation (t = 2.128, p = .042). Participants in the control group revealed no significant changes. Comparing the mean differences in pre- and posttest scores between yoga and control groups, we found the yoga group significantly decreased work-related stress (t = -3.216, p = .002), but there was no significant change in stress adaptation (p = .084). While controlling for the pretest scores of work-related stress, participants in yoga, but not the control group, revealed a significant increase in autonomic nerve activity at midpoint (6 weeks) test (t = -2.799, p = .007), and at posttest (12 weeks; t = -2.099, p = .040). LINKING EVIDENCE TO ACTION: Because mental health professionals experienced a reduction in work-related stress and an increase in autonomic nerve activity in a weekly yoga program for 12 weeks, clinicians, administrators, and educators should offer yoga classes as a strategy to help health professionals reduce their work-related stress and balance autonomic nerve activities.