The COVID-19 pandemic disrupted several routine teaching methods in clinical settings which causing psychological distress among medical students. This study aims to explore the association of perceived stress related to the adapted medical education, resilience, and depression among medical students at a medical school in northern Thailand during the COVID-19 outbreak. A total of 437 medical students were recruited in January 2022. Data were obtained using self-administered online questionnaires, including demographic data, perceived challenges in learning online classes, the Resilience Inventory (RI-9), and the Patient Health Questionnaire 9 (PHQ-9). Binary logistic regression analysis was employed to explore factors associated with depression (PHQ-9 ≥ 9). A total of 27% of the participants were identified as having depression. Logistic regression revealed that the presence of previous psychiatric conditions (ß = 2.80, p < 0.05), stress from lack of in-person contact with peers (ß = 1.48, p < 0.05), stress from lack of in-person communication with teachers (ß = 1.49, p < 0.05), and level of resilience (ß = 0.88, p < 0.001) were independently associated factors for depression among medical students. Level of resilience was negatively correlated with depressive symptoms (r = −0.436, p < 0.001). The rate of depression among medical students was higher during the pandemic. Resilience was associated with depression. Strengthening resilience might have an important implication for depression among medical students.