Compared with able-bodied (AB), people with spinal cord injury (SCI) have a 3- to 5-fold higher risk of developing type 2 diabetes mellitus, which may be associated with increased fat mass. Evidence suggests that leptin regulates body adiposity through the sympathetic nervous system, which is impaired in people with high lesion SCI. The purpose of this study was to determine the relationship among leptin levels, body composition, and resting metabolic rate (RMR) in people with high lesion SCI and body mass index-, weight-, height-, and waist circumference-matched AB subjects. Fourteen subjects (seven SCI and seven AB) participated in the study. After an overnight fast, various hormones, glucose, and RMR were measured. There was no significant difference in plasma glucose, insulin, GH, cortisol, and glucagon levels between the two groups. The SCI group had 105% higher plasma leptin levels than the AB group (P < 0.05). Plasma leptin levels correlated with body mass index (SCI: r = 0.80; P = 0.028; AB: r = 0.79; P = 0.035) and fat mass (SCI: r = 0.95; P = 0.001; AB: r = 78; P = 0.038) in both groups. The plasma leptin level correlated with the absolute RMR (SCI: r = 0.15; P = 0.75; AB: r = 0.99; P < 0.006) and the RMR per unit fat-free mass (SCI: r = -0.70; P < 0.08; AB: r = 0.845; P < 0.017) in the AB group, but not in the SCI group. The absolute RMR was significantly reduced in the SCI group compared with the AB group, but there was no difference in the relative RMR between the groups. In conclusion, the SCI group has a significantly higher plasma leptin level than the AB group. The absolute and relative RMR correlated with leptin only in the AB group.