ObjectivesThe purpose of this non interventional study was to define changes in anxiety, depression, and sleep quality of medical students in their first two years of medical school while considering potential risk factors of self-reported chronic disease, sleep quantity, year of medical school and exercise habits. Since this study was ongoing during the COVID-19 pandemic, its effect was also evaluated. Participants/METHODS: A cohort of 197 medical students was evaluated longitudinally using survey methods to quantify changes from pre-medical school and summer break to each semester in medical school throughout years one and two. This study was performed from July 2019 through June 2021. Data was analyzed using Generalized Linear Mixed Models (GLMMs) on the numeric responses of General Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Sleep Quality (SQ-3) and Pittsburg Sleep Quality Index (PSQI). Additional assessments evaluated exercise habits, chronic disease, and impact of COVID-19 Pandemic. The COVID-19 Pandemic was evaluated directly in the model (pre- and post-COVID-19 period variable), and through additional questions on their perceived effect. ResultsDepression, anxiety, and sleep habits displayed a cyclical change that was associated with the academic/seasonal cycle. The COVID-19 pandemic was never found significant. Medical students who had a chronic disease diagnosis and fewer hours of sleep had increased severity. Exercise did not play a role. ConclusionBased on our sample, the main driver for depression, anxiety, and poor sleep quality appears to be the academic/seasonal cycle, while the COVID-19 pandemic did not have an impact on mental health.