Background: COVID19 pandemic had a huge impact on global mental health. Health students, because of their age and status, are a more at-risk population. National survey during the first wave already found high levels of psychological distress. Objective: This nationwide study aimed to assess health's student mental health during the third wave in France. Methods: We did an online national cross-sectional study, which addressed all health students from April 4th to May 11th 2021. The questionnaire included sociodemographic and work conditions questions, Kessler 6 scale, and numeric scales. Results: 16,937 students answered, including 54% nurse and 16% medical students. Regarding K6 scale, 14% have moderate (8-12) and 83% high (≥13) level of psychological distress. In multivariate analysis, being a man (OR = 0.54, 95% CI [0.48; 0.60], p < 0.001) and not living alone (OR = 0.71, 95% CI [0.62; 0.82], p < 0.001), are associated with a reduced risk of psychological distress. Not having the ability to isolate themselves (OR = 1.58, 95% CI [1.39; 1.81], p < 0.001), and having low (OR = 2.31, 95% CI [2.08; 2.56], p < 0.001) or important (OR = 4.58, 95% CI [3.98; 5.29], p < 0.001) financial difficulties are associated with an increased risk of psychological distress. Limitations: The response rate was low regarding the target population (300,000 health students). Conclusion: Compared to the first national survey, we noticed mental health deterioration. Psychological distress (83% high level versus 21%), substance use (21% versus 13%), and psychotropic treatment use (18% versus 7.3%) hugely increased. These results highlighted the need to increase support actions for health students.