Context In March 2020, the World Health Organization declared the novel coronavirus disease 2019 (COVID-19) outbreak a pandemic. Due to the rapid spread, strong contagion, high incidence of lethality in severe cases, and the lack of a pharmaceutical prevention or cure, COVID-19 has posed a serious threat to human life and health. It has also had a tremendous impact on mental health, including fear and worry, difficulty sleeping or concentrating, and increased use of poor coping mechanisms. Osteopathic medical students have had additional concerns regarding the interruption of their studies, closing of clinical rotations, and postponed licensing exams. To date, few reports have focused on osteopathic medical students and their reactions to the outbreak. Objectives To assess resilience, coping, health behaviors, and emotional wellbeing of osteopathic medical students during the onset of the COVID-19 pandemic. Methods In this cross-sectional study, we distributed an anonymous online survey to all medical students enrolled at Nova Southeastern University in May 2020 (n=1,310) via an e-mail invitation using the institution’s student listservs. Our major study variables were based on published reports and anecdotal evidence; we subsequently developed the Emotional Wellbeing in Healthcare Professions Students Questionnaire (EWB-Q). This EWB-Q contained validated scales to assess the contribution of levels of coping strategies used, personal resilience, and health behaviors on the emotional wellbeing of osteopathic medical students. Multiple linear regression and other statistical analyses were conducted using SPSS v0.26. Results Of the 1,310 students invited to participate, 335 (25.5%) surveys were returned. Of those, 133 had more than 33% of the necessary data missing and were removed, resulting in 202 (15.4%) completed questionnaires. The mean age of the participants was 26.7 years. About half (n=92; 45.5%) were in the clinical phase (years 3 and 4) of their medical school training (in rotations). A significant regression equation was found (F[4,171]=17.481, pR 2 =0.290, R 2adjusted=0.274), indicating that levels of coping, personal resilience, and health behaviors (i.e., not sleeping more than usual, not exercising less than usual) accounted for a significant amount of the variance in emotional wellbeing scores in osteopathic medical students. Higher levels of resilience, greater use of coping strategies, not sleeping more than usual, and not exercising less than usual were predictors of emotional wellbeing. Conclusions Cultivating positive mental health should be a high priority for medical educators as they develop and implement curriculum-based initiatives to help medical students bolster their personal resilience and to encourage healthy coping behaviors during times of crisis and beyond. A proactive position that assists with building personal resilience and developing stress management habits is paramount in assisting students who are grappling not only with the challenges of rigorous medical training, but also with the uncertainty and stress that exists during any major global health or socioeconomic crisis.