IntroductionStudents are at risk for mental health issues due to the COVID-19 pandemic. The implementation of lockdowns as a means to curb the spread of the disease have had an impact on this population, as observed in many international studies. However, few studies have investigated the longitudinal impact of COVID-19 lockdowns on students’ mental health. ObjectiveWe explored the relation between individual characteristics of students, context of life, difficulties in emotion regulation and psychological distress over the first two lockdowns in France during the COVID-19 pandemic. Methodology160 university students (90% female, mean of 24 years old) responded to an online questionnaire at three times points: once during the first lockdown during the COVID-19 pandemic in march 2020, a second time after this lockdown and a third time during the second lockdown. Difficulties in emotion regulation, psychological distress, acute stress, academic concerns, financial resources, and exchanges with professors were measured. ResultsAn exploratory structural equations model was developed to investigate the factors related to psychological distress (χ2=1459.18, df=1064, CFI=0.910, RMSEA=0.049, SRMR=0.068). During both lockdowns, psychological distress was explained by academic concerns and lack of emotional clarity and acceptance. An indirect and negative significant relation was identified between financial difficulties, lack of exchanges with professors during the first lockdown, emotion clarity and experienced psychological distress during the second lockdown. Repeated measures ANOVAs identified high levels of acute stress during both lockdowns and a diminution during the deconfinement indicating an impact of sanitary measures on student's mental health. ConclusionCoherently with the Bruchon-Sweiser translational model of stress, emotion regulation capacities seem to have a central and moderating role in the experience of the pandemic for students. They would benefit greatly from appropriate therapeutic interventions in this pandemic situation and in general.