Abstract Introduction On March 17, 2020, in Reunion Island, the lockdown was established for 8 weeks in order to limit the spread of the virus responsible for the COVID-19 pandemic. Beyond the beneficial aspects on the control of the infectious risk, questions arose around the repercussions of this universal preventive measure on the mental health of the Reunioneses. The objective of the study was to describe the impact of lockdown measures on the stress level of the adult population of Reunion Island and factors associated with changes in stress level. Methods Cross-sectional KABP-type study ‘Confinaou’ in general population (≥ 18 years), by online self-questionnaire accessible during the first lockdown, from April 30 to May 10, 2020. To identify the independent predictive factors of the increase in stress felt during lockdown, we performed a multivariate logistic regression. Results The analysis included 1,421 adults, of whom 706 (49.7%) reported an increase in lockdown-related perceived stress compared to baseline state. Factors independently associated with increased stress level were being female (OR = 1,33 [IC à 95%: 1,02-1,72]) and, living in crowded housing (OR = 1,30 [IC à 95%: 1,03-1,68]). Factors associated with reduced stress level were being 60 years of age or older (OR = 0,65 [IC à 95%: 0,45-0,95]) and feeling well or completely informed about Covid-19 prevention measures and lockdown rules (OR = 0,75 [IC à 95%: 0,58-0,96]). Conclusions This study confirms that psychological repercussions can occur in the population during lockdown as observed in the Reunionese population of the study. A targeted and adapted preventive public health response could be considered to prevent the mental repercussions of such situations of isolation and restriction of social interactions in the general population. Women, and youth could be a priority for prevention interventions using health literacy improvement approach. Social equality policy measures could focus on housing conditions. Key messages • Targeted mental health prevention actions adapted to at-risk populations (women, young people, people in precarious housing situations) have to be set up in these isolation situations as the lockdown. • Prevention actions will have to integrate actions to improve communication and ‘crisis information’ to prevent the negative impacts of a new pandemic on mental health.