ObjectiveTo examine the relationship between physical activity, sedentary behaviors, and social isolation in a representative sample of Brazilian adolescents. MethodCross sectional analyses using data from the Brazilian Scholar Health Survey conducted in 2015. The sample included 100,839 adolescents (mean age: 14.3 y, 51.4% Female) from 3040 schools. Information about social isolation (number of close friends and perceived loneliness), physical activity (International Physical Activity Questionnaire) and sedentary behaviors (total sitting time and TV viewing) were self-reported. Chronological age, race and type of city (state capital or other) were co-variables. Logistic regression models were used to analyze the data (results are presented as odds ratios (OR) with 95% confidence intervals). ResultsPhysical activity was associated with lower odds of both social isolation indicators in boys, and with lower likelihood of having few friends in girls. Greater sitting time was associated with higher likelihood of social isolation, as was low (<1 h/d) [boys: OR: 1.54 (95% CI: 1.33 to 1.77); girls: OR: 1.31 (95% CI: 1.17 to 1.48] and high TV viewing (≥8 h/d) [boys: OR: 1.75 (95% CI: 1.47 to 2.09)]; girls: OR: 1.58 (95% CI: 1.37 to 1.82)]. More than 300 min/week of physical activity was sufficient to eliminate the association of high TV viewing and high sitting time with markers of social isolation in boys. ConclusionPhysical activity is associated with a lower prevalence of social isolation, especially among boys. Both high and low amounts of TV viewing increase the likelihood of social isolation. Physical activity reduced the association between TV viewing and sitting with social isolation among boys.