The aim of this study was to analyse the contribution of social support from family, friend and school (teacher and classmate) contexts in substance use (tobacco and alcohol use) and well-being (life satisfaction and health-related quality of life). Participants were 5,784 Portuguese and 22,610 Spanish adolescents aged 11 to 16 years, from the 2014 edition of the Health Behavior in School-aged Children (HBSC) study in Portugal and Spain. Results showed that for a higher life satisfaction,

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... (p < .001, partial η2 = .032), teacher (p < .001, partial η2 = .018) and classmate (p < .001, partial η2 = .031) support were important in Portugal, and family (p < .001, partial η2 = .056) and friend (p < .001, partial η2 = .015) support in Spain. Similarly, for a better health-related quality of life, all the social support variables were relevant in Portugal (family: p < .001, partial η2 = .063; teacher: p < .001, partial η2 = .032; classmate: p < .001, partial η2 = .054; friend: p < .001, partial η2 = .034) and in Spain (family: p < .001, partial η2 = .054; teacher: p < .001, partial η2 = .014; classmate: p < .001, partial η2 = .018; friend: p < .001, partial η2 = .040). In contrast, only family support (p < .001, partial η2 = .014) was relevant in Portugal for tobacco use. Therefore, social support was more relevant for adolescent well-being than for adolescent substance use, and the most relevant source of support was family support, in both Spain and Portugal.