Numerous research results have already pointed towards the negative influence of increased mental stress on educational processes and motivational criteria. It has also been shown that the global public health crisis induced by COVID-19 was related to anxiety symptoms and elevated levels of distress. To holistically elucidate the dynamics of the pandemic-related mental stress of first-year medical students, the associated parameters of three different cohorts were measured at the beginning of the pandemic-related restrictions on university life in Germany (20/21), at the peak of the COVID-19-related restrictions (21/22) and during the easing of the restrictions in the winter term 22/23. In a repeated cross-sectional study design, the constructs of worries, tension, demands and joy were collected from first-year medical students (n= 578) using the Perceived Stress Questionnaire. The results demonstrate significantly increased values of the constructs worries (p< 0.001), tension (p< 0.001) and demands (p< 0.001) at the peak of the pandemic related restrictions compared to the previous and following year as well as significantly decreasing values of general joy of life during the observed period of 3 years (allp-values < 0.001). A confirmatory factor analysis was performed to verify the questionnaire’s factor structure regarding the addressed target group during the pandemic (CFI: 0.908, RMSEA: 0.071, SRMR: 0.052). These data, collected over a period of three years, provide information regarding dynamically manifesting mental stress during the COVID-19 pandemic, and refer to new areas of responsibility for the faculties to adequately counteract future crisis situations.