OBJECTIVES: This study was conducted to investigate the prevalence of mental health (MH) symptoms and associated factors among medical students who were engaged in combating the coronavirus disease 2019 (COVID-19) epidemic in 4 provinces/cities of Vietnam. METHODS: A cross-sectional study with 580 participants was conducted at a medical university in Northern Vietnam. MH was assessed using the 21-item Depression, Anxiety, and Stress Scale, which was previously standardized in Vietnam. Data were collected through a structured self-administered questionnaire. Multivariate logistic regression was employed to examine the association between MH symptoms and relevant factors. RESULTS: Out of a total of 2703 medical students, 21.5% responded to the questionnaire. Among the 580 respondents, the prevalence rates of depression, anxiety, and stress were 43.3%, 44.0%, and 24.7%, respectively. Factors significantly associated with self-reported depression included being female and having a COVID-19 infection. Similarly, being female and having a COVID-19 infection were significantly associated with self-reported anxiety. Factors associated with self-reported stress included being female, having a personal or family history of MH symptoms, working more than 8 hr/day, and having a COVID-19 infection. CONCLUSIONS: COVID-19 has adversely impacted the MH of medical students. Our findings are valuable in their potential to motivate universities, MH professionals, and authorities to offer mental healthcare services to this group. Furthermore, there is a pressing need for training courses designed to equip future healthcare workers with the skills to manage crises effectively.