The coronavirus disease 2019 outbreak has impacted many educational institutions by imposing restrictions on offline or in-person lessons. Many students were stressed by “the loss of everyday life” due to the pandemic, and it is important to examine the impact of this loss on adolescents’ mental health. This study aimed to investigate the factors that affect students’ mental health during the pandemic from various perspectives. A total of 166 medical students participated in this study. Participants completed questionnaires about their demographics, life stress, mental health, and stress factors during in-person and online lecture days. Participants were divided into 2 groups, those with low and high mental health. The researchers compared independent variables between the groups using the χ2 test or Fisher’s exact test. Multiple logistic regression analysis was performed, with mental health as the dependent variable. The multiple logistic regression analysis indicated that increased time spent online was significantly associated with mental health (P < .05). Human relations and the inability to meet/talk with friends trended toward a significant association with mental health (P < .1). The students who were not stressed about the increased time spent online were at a risk of low mental health. The students who appreciated interacting with others experienced more stress during the lockdown. To reduce students’ stress on online days, teachers should devise a lecture style with frequent breaks and introduce active learning. The findings of this study will contribute to addressing students’ low mental health and reducing their stress during the coronavirus disease 2019 pandemic.