Purpose: This study examined the association between physical activity (PA), physical fitness, and health-related quality of life (HRQOL) among school-aged children. Methods: Participants were 201 children (91 boys, 110 girls; M[subscript age] = 9.82) enrolled in one school in the southern US. Students' PA (self-reported PA, pedometer-based PA) and physical fitness (cardiorespiratory fitness, muscular fitness, flexibility, and body composition) were assessed in the fall. The PedsQL™ 4.0 (Varni et al., 2001) was used to assess participants' HRQOL (physical and mental function) in the spring. Results: PA and four components of physical fitness were positively associated with physical and mental function. Path analyses suggested physical fitness mediated the relationship between self-reported PA and HRQOL (95% CI: [0.53, 1.48]), as well as between pedometer-based PA and HRQOL (95% CI: [0.54, 1.53]). Discussion: Results support the conclusion that enhancing children's physical fitness can facilitate positive outcomes including improved health related quality of life.