Background: Little is known regarding how dimensions of the family social environment relate to fitness levels and physical activity self-efficacy (PASE) among adolescents who are overweight or obese and whether these relationships are mediated by self-esteem. Methods: Potential associations were evaluated between relationship subdomains (cohesion, conflict, expressivity) of the Family Environment Scale (FES), self-esteem (Rosenberg Self-Esteem Scale, RSES), and PASE and fitness, using recovery heart rate [RHR, beats per minute (bpm)] from a 3-minute submaximal step test at baseline. Participants were 108 adolescents who were overweight or obese and were seeking weight-loss treatment as part of the Healthy Kids, Healthy Weight 12-week multidisciplinary pediatric weight management program. Structural equation modeling (SEM) was used to simultaneously evaluate paths between these variables and test for mediation. Results: In multivariable models, higher FES cohesion (beta = -2.18, s.e.= 0.98; p = 0.02), expressivity (beta=-1.97, s.e.=0.99; p<0.05), and PASE (beta=-0.64, s.e.=0.33; p<0.05) scores were associated with lower RHR, which represents higher fitness. Furthermore, higher FES conflict scores were associated with lower RSES scores (beta=-0.83, s.e.=0.29; p<0.01), and FES conflict (beta=-0.63, s.e.=0.22; p<0.01) and RSES (beta=0.33, s.e.=0.07; p<0.01) were associated with PASE scores. In a good-fitting multivariate SEM [Comparative Fit Index (CFI)=1.00; Standardized Root Mean Square Residual (SRMR)=0.02; Tucker-Lewis index (TLI)=1.22; Root Mean Squared Error of Approximation (RMSEA) <0.01], RSES mediated the relationship between FES conflict and PASE (sum of indirect paths: beta=-0.30, s.e.=0.11; p<0.01) scores. Conclusions: Our results highlight the importance of the relationship domain of the family environment on self-esteem, PASE, and physical fitness in adolescents who are overweight or obese.