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Background: Increasing attention is being paid to medical students' mental wellbeing globally due in part to their exposure to stressors inherent in medical education and the numerous reports of elevated rates of mental health conditions in this population. Aims: This study aimed to identify stressors and determine prevalence rates of psychiatric morbidity, substance use and burnout in a sample of Nigerian medical students. Methods: In a cross-sectional online survey, 505 medical students from 25 Nigerian medical schools completed a socio-demographic questionnaire, short version of the General Health Questionnaire (GHQ-12), the CAGE questionnaire and the Oldenburg Burnout Inventory (OLBI). Result: The most commonly reported sources of stress were study (75.6%), money (52.3%) and relationships (30.1%). Nine students (1.8%) had received a mental health diagnosis prior to medical school but this number had increased to 29 (5.7%) whilst in medical school, with the majority being cases of anxiety and depressive disorders. The prevalence of psychological distress was 54.5%, but <5% of affected students had received any help for their mental health conditions. Twenty five students (5%) met criteria for problematic alcohol use and 6% had used cannabis. The proportions of students who met criteria for disengagement and exhaustion domains of the OLBI were 84.6% and 77.0% respectively. Conclusion: The prevalence of psychological distress and burnout is high among medical students. Interventions for medical students' well-being should be tailored to their needs and should target risk factors related to personal, organisational and medical school academic structure attributes.