Studies show greater physical activity levels and fewer sedentary behaviors are associated with better overall health-related quality of life (HRQOL) in youth. However, because the samples were comprised of Caucasian youth, the generalizability of these findings is limited. This study assesses the associations among physical activity, sedentary behaviors, and HRQOL in Hispanic 3rd through 5th grade students (N=448), who completed the PedsQL 4.0 Generic Core Scales and the School Physical Activity and Nutrition questionnaire. Anthropometric skinfold measurements were taken to compute body fat percentage. Multiple linear regression analysis was conducted with each of the PedsQL domains: physical, emotional, social, and school functioning, and total HRQOL, which were entered as separate dependent variables. Participating in sports teams in the last 12 months was associated with better physical and social functioning and total HRQOL. Greater number of hours watching TV was associated with lower physical and emotional functioning and total HRQOL. Number of hours playing video games was not significantly associated with any of the HRQOL domains. These findings have implications for the development of interventions to enhance the HRQOL in 3rd through 5th grade Hispanic youth by targeting participation in organized sports and minimizing TV watching.