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Objective: The aims of the present study were to analyze the associations between the socio-demographic and familiar circumstances with: (i) the total leisure-time sedentary behavior (SB) assessed by accelerometry, and (ii) the domain-specific leisure-time SB (i.e., screen-based, educational-based, social-based, and other-based SB), in a sample of Spanish youth. Method: The sample consisted of 1,543 youth (12.02 ± 2.51 years) included in the UP&DOWN study. SB was evaluated by accelerometry and questionnaire. Nationality, location of school, type of school, socio-economic status, parental educational level, parental occupation status, family structure, number of siblings and position among siblings were self-reported by participants or their parents. Linear mixed models, including school and city as random effects, were performed. Results: Several associations were found; however, socio-demographic and family circumstances differently associated with SB according to the domain-specific SB, the sex and the type of day. For example, participants with a father holding a high-skilled occupation spent lower time in screen-based SB during weekdays; and mother occupation status of high qualification was related to higher educational-based SB in boys. Having three or more sibling was associated with lower total SB in boys, while having an obese mother was related to higher screen-based SB on weekends both in boys and girls. Conclusions: Socio-demographic and familiar circumstances are associated with SB in young people, so future interventions should consider multiple and sex-specific factors for reduce SB of young people, focusing especially on youth with a low number of siblings and with parents holding low-skilled employments. [ABSTRACT FROM AUTHOR]