Objectives: Physical exercise has an important role in reducing body fat, risk of chronic disease and systemic inflammation. The aim of this study was to determine serum leptin and insulin concentrations and their relationship to the time of physical exercise after injury in men with cervical spinal cord injury (c-SCI). Methods: c-SCI subjects with lesion level in C5-C7 (n ¼ 25) were divided into two groups: physically active (PA, n ¼ 13; those who practiced physical exercise for at least 3 months, three times per week or more, for a total minimum of 150 min of physical activity per week) and non-physically active (N-PA, n ¼ 9). Body composition was assessed by dual energy X-ray absorptiometry. Blood samples were obtained 12 h after an overnight fast to measure insulin and leptin in serum, and glucose and C-reactive protein (CRP) in plasma, by validated methods. Results: Comparing the PA and N-PA group, the first presented lower: total body mass ( À13%), body mass index ( À16%), fat mass (kg À39%, FM% À30%), CRP ( À23%), serum insulin ( À61%), homeostasis model assessment (HOMA, À35%) and serum leptin ( À62%; Po0.05). Both serum insulin (r ¼ À0.561; Po0.05) and HOMA (r ¼ À0.591; Po005) were inversely proportional to the time of practice of physical activity after injury. Conclusion: Our results suggest that exercise was able to reduce fat mass and increase insulin sensitivity, decreasing plasma levels of risk factors in c-SCI subjects.