Abstract Background The surge of COVID-19 infections has prompted many countries to take unprecedented policy measures. In Belgium, the authorities implemented a nation-wide stay-at-home order for several months. Evidence of the mental health effect of such measures is scarce. A recent review by Brooks et al. has compiled a defined list of stressors affecting people’s mental health under quarantine during previous epidemic settings. This study aims to test the association between these stressors and the mental health of students attending higher education during the stay-at-home order in Belgium. Methods In this cross-sectional study, 18,301 students from 13 higher education institutions (HEI) participated in an online survey between 26 April and 11 May 2020. We assessed the association between potential stressors and depressive symptoms severity scores and structural equation modeling was used to assess how stressors may mediate the association between duration of exposure and depressive symptoms severity. ...