Objective: To identify stress management practices and examine the impact of the COVID-19 pandemic on well-being among male and female physician assistant (PA) students. Participants: Participants included 1,239 students from nine PA programs who matriculated pre-pandemic, acute pandemic, or post-acute pandemic. Methods: Measures included questions about stress management practices and validated instruments assessing perceived stress, life satisfaction, and psychological flexibility. Data were analyzed for differences based on year and gender. Results: Exercise (91.6%), yoga (54.6%), meditation (34.3%), and journaling (32.5%) were commonly reported stress reduction practices. Newly matriculated PA students adjusted to the COVID-19 pandemic differently based on gender. Pre-pandemic, men and women reported similar levels of perceived stress and psychological flexibility, but female students reported higher life satisfaction. Post-acute pandemic, however, female students reported higher perceived stress and lower psychological flexibility. Conclusions: Wellness resources may be strengthened by approaches that account for differences based on gender.