Study design: Cross-sectional design. Objectives: This study examined the relationships between circulating adiponectin levels, body composition, metabolic profile, and measures of skeletal muscle mitochondrial enzyme activity and biogenesis. Settings: Clinical Research in a Medical Center. Methods: Plasma adiponectin was quantified in 19 individuals with chronic spinal cord injury (SCI). Body composition was evaluated by dual x-ray absorptiometry and magnetic resonance imaging. Metabolic profile was assessed by basal metabolic rate (BMR), oxygen uptake (VO2), and intravenous glucose tolerance testing. Mitochondrial enzyme activity of skeletal muscle was obtained by spectrophotometric assays and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and 5′ AMP-activated protein kinase (AMPK) protein expression was assessed by Western blots. Results: Adiponectin was negatively related to both total and regional fat mass and positively related to lean mass and muscle mass. Furthermore, there were positive relationships between adiponectin and BMR (r = 0.52, P = 0.02) and VO2 (r = 0.73, P = 0.01). Furthermore, adiponectin was positively related to citrate synthase (r = 0.68, P = 0.002) and complex III activity (r = 0.57, P = 0.02). The relationships between adiponectin and body composition remained significant after accounting for age. The relationships between adiponectin, metabolic profile, and markers of mitochondria mass and activity were influenced by age. Conclusions: The study demonstrated that adiponectin is closely related to body composition and metabolic profile in persons with SCI and further supports mechanistic studies suggesting that adiponectin may stimulate mitochondrial biogenesis.