Purpose: The impact of the coronavirus disease 2019 crisis on medical education includes reduced clinical training, a significant loss of learning time and a probable decline in confidence of being a doctor. These recent changes will have significant effect on the well-being of medical students and interventional support needs to be given early. This study explores the challenges faced and coping strategies used by preclinical medical students during the crisis. Methods: A qualitative study involving 13 preclinical medical students was conducted between August and September 2020 at a medical school in Malaysia. An in-depth individual interview via Microsoft Teams (Microsoft Corp.) with semi-structured questions was conducted. The recorded interview data were thematically analyzed using the six phases of Braun and Clarke’s Thematic Analysis. Results: The challenges faced were identified under three themes: psychosocial impact of lockdown, significant lifestyle changes, and impact on professional progression. Meanwhile, four themes emerged in coping strategies that include behavioral strategies, re-appraisal of the uncertainties of situation, active coping mechanisms, and regulation of emotion with coping reserve. There are indications that personality traits determine strategies to cope with challenges faced during the crisis which may either lead to resilience building or experiencing burnout. Conclusion The findings of the study highlighted the urgent need to develop early preventive and intervention strategies to address the mental health of medical students to mitigate stress and promote positive well-being in times of crisis.