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Wellbeing declines during adolescence, for which the reasons are unclear. This analysis explored associations between wellbeing and multiple lifestyle, socioeconomic and school-level factors in young people. Data were collected as part of the Wellbeing in School (WiSe) survey of adolescent school children in Northern Ireland at age 13–14 years ( N  = 1618; 49% female) and 15–16 years ( N  = 1558; 50.5% female). Wellbeing was assessed using the short-form Warwick-Edinburgh Mental Wellbeing Scale (sWEMWBS), where scores declined between time one (13–14 years) and time two (15–16 years) in both sexes and were significantly lower in females at both timepoints. Multilevel, multivariate modelling was therefore undertaken separately for males and females with sWEMWBS scores as the dependent variable. Physical activity, family affluence, fruit and vegetable intake, social media use, sleep duration, school factors (size and type) and religion were independent variables. More frequent physical activity in both sexes at both timepoints was associated with higher sWEMWBS scores. In females, higher sWEMWBS scores were associated with less social media use at time one (and marginally at time two), greater family affluence at time two, and being Catholic at both timepoints. In males, higher sWEMWBS scores were associated with more frequent fruit and vegetable intake at time one. Mental wellbeing was unrelated to sleep duration or school factors in either sex, at both time points. Efforts to maximize mental wellbeing in adolescents should promote engagement in physical activity and implement sex-specific interventions.

Less Screen Time, More Frequent Fruit and Vegetable Intake and Physical Activity are Associated with Greater Mental Wellbeing in Adolescents