The recent worldwide health pandemic and related social distancing and restrictions negatively impacted adolescents' mental health, including depression, underscoring the need for comprehensive understanding beyond immediate impacts. We aimed to identify factors assessed during the first and second lockdowns that were associated with depression symptoms 2 years after restrictions easing. This study included 1,946 adolescents, aged 15-18 years, involved in the French Epidémiologie et Conditions de Vie population-based cohort. Depression symptoms were assessed twice, with the nine-item Patient Health Questionnaire, at the beginning of restrictions easing and 1 year later. Logistic regressions were used to estimate associations among sociodemographic, socioeconomics, health, substance use, lockdown conditions, and pandemic-related factors, self-reported during the first and second lockdowns in France, and depression symptoms. Elastic-Net regression was used to study the joint effect of characteristics assessed during both lockdowns. A total of 472 (25.25%) adolescents reported depression symptoms in the restrictions easing period, 369 (78.18%) were girls and 103 (21.82%) were boys. Factors associated with a higher risk of reporting depression symptoms included being a girl, a smoker, frequently consuming alcohol, having spent lockdowns in a place without outdoor space, poor perceived health, and pre-existing mental disorders. Factors associated with depression symptoms after restrictions easing were well known and mostly not related to social distancing and restrictions, suggesting that already vulnerable youth were more likely to be impacted by the stressful pandemic context. Special caution is needed for these adolescents to limit pandemic's impact on long-lasting mental health. These results also underscore the importance of early identification of at-risk adolescents and the development of interventions to enhance their resilience and support in case of future crises.Read less <