To investigate the prevalence and determinants of burnout syndrome and depression among medical students at Unaizah College of Medicine (UCM), Qassim University, Qassim, Kingdom of Saudi Arabia (KSA). Methods: A cross-sectional study of all Saudi medical students studying at UCM, Qassim University, Al Qassim, KSA, between February to March 2020. Results: Of the total 305 students sampled, 153 (50.2%) fit the category of depression. Concerning burnout, only 5.6% of the total population met the Maslach Burnout Inventorydiagnostic criteria for burnout, with those determined to have burnout having ranked high on the emotional exhaustion and cynicism subscales, and low on the academic efficacy subscale. Male was strongly associated with burnout, while female gender and raising children were strongly associated with the presence of depression. Emotional exhaustion and high cynicism as determinants of burnout elevate the risk of depression. Conclusion: Our results highlight the high rate of depression and burnout, as well as the need for psychological intervention programs at medical schools to prevent the deterioration of student's mental health that has been associated with advancement in medical school.