Background: Studies have highlighted the impact of the COVID-19 pandemic on the mental health of university students. However, little is known about the psychological impact of successive lockdowns on this population. Objectives: To assess the prevalence of psychological distress in a student population during the first two lockdowns linked to the COVID-19 pandemic, and to stratify them by subgroup. Methods: We used a repeated cross-sectional study of a university student population in France during the first lockdown, the unlockdown, and the second lockdown. We measured rates of depression, anxiety, distress and suicidal ideation. A weighted prevalence was calculated with 95% confidence intervals. Predictors of symptom progression were measured using adjusted logistic regression. Results: 19,150 university students responded to the surveys. Our results suggest a significant decrease in the scores for depression (aOR = 0.64; CI%: 0.59–0.70), anxiety (aOR = 0.81; CI%: 0.74–0.88), and distress symptoms (aOR = 0.47; CI%: 0.43–0.51) between the first lockdown and the lifting of the lockdown. However, a significant increase in symptoms of depression (aOR = 1.53; CI%: 1.43-1.64), anxiety (aOR = 1.56; CI%: 1.45–1.67) and suicidal ideation (aOR = 1.59; CI%: 1.45–1.73) between the first and second lockdown is highlighted. The most impacted students are PhD students, they show a significant increase (aOR = 4.37; CI%: 1.41–13.54) in suicidal ideation. Conclusion: Mental health professionals will need to be vigilant about this population, both to provide care for psychological distress, but also to reduce the risk of PhD students dropping out. HIGHLIGHTS Successive lockdowns have a significant impact on the mental health of university students. PhD students have experienced the most significant deterioration in their mental health. The rate of suicidal ideation has increased significantly across the university student population.