Introduction: The aim of the study is to determine the changes in psychological distress and depressive symptoms of medical students in the first two years of their education process, in comparison with other faculty students. Methods: All first-year students in the Faculties of Medicine, Economics and Sport Sciences were asked to fill out a detailed self-reported questionnaire aimed at measuring possible stressful life events and habits, General Health Questionnaire (GHQ-12), Beck Depression Inventory (BDI) during the first week of their first semester in 2017–2018. This process was repeated to the same students again in the second year, and the change was examined prospectively. Results: The GHQ-12 score average increased from 11.19 to 13.7 in medical students (p<0.001). The prevalence of psychological distress increased from 53.8% to 61.8%. The BDI score average was 8.04 in the beginning and reached 10.1 in the second year (p<0.001). Depressive symptom prevalence increased from 8.8% to 19.5%. No significant increase was observed in the GHQ-12, BDI score average, depressive symptoms, and psychological distress prevalence of other faculty students. The incidence of depressive symptoms in medical students was 15.9%. As a result of multivariate analysis, “dissatisfaction with social activities” and “exposure to psychological pressure and violence” which were stressful life events were statistically associated with both GHQ-12 and BDI. Conclusion: It was determined that the mental health of the students was negatively affected in the first year of medical school education. It is recommended to raise awareness for medical students at risk of mental illness and to plan interventions that will protect their mental health.