Parameters of body composition and leisure-time physical activity (LTPA) may serve as predictors of quality of life (QOL) after spinal cord injury (SCI). However, we are unaware of any studies that have conducted a detailed assessment of body composition using sophisticated imaging techniques and established associations with the domains of QOL. Determining this association will provide an understanding of how QOL may impact longitudinal intervention trials. PURPOSE: To examine the relationships between QOL domains in persons with SCI and their levels of weekly LTPA, anthropometrics, and body composition assessment compartments. METHODS: Exploratory cross-sectional study of baseline data collected as part of a randomized clinical trial. A convenience sample of 36 community-dwelling persons with SCI participated in the current study. OUTCOMES: Outcome measures included the World Health Organization Quality of Life Short Form (WHOQOL-BREF), Leisure-Time Physical Activity Questionnaire for People with Spinal Cord Injury (LTPAQ-SCI), anthropomorphic measures (waist, hip, and abdominal circumference), and dual-energy x-ray absorptiometry to quantify regional and total body composition. RESULTS: Multiple regression models suggested that engagement in LTPA explained 35.7% of the variance in physical health QOL (p < 0.05), 33.5% in psychological QOL (p < 0.10), and 38.2% in environmental QOL (p < 0.05). Anthropometric measures and regional and total body composition assessments did not demonstrate predictive capability, which may be due to the small sample size. Within these models, the number of minutes of heavy LTPA per day uniquely predicted physical health QOL (p < 0.01), and the number of mild LTPA days per week uniquely predicted psychological QOL (p < 0.05). Bivariate analyses also suggested that android fat and supine waist circumference were positively associated with the social domain of QOL (p < 0.05). CONCLUSIONS: Encouraging individuals with SCI to engage in LTPA may enhance multiple aspects of QOL while reducing the risk for cardiovascular and metabolic morbidities associated with SCI.