Individuals with traumatic spinal cord injury (SCI) are extremely inactive yet little is known about the long-term consequences of chronic inactivity. Current research investigated the concentrations of high density lipoprotein cholesterol (HDLc) and its subfractions HDL2 and HDL3 in 66 extremely sedentary SCI admissions to a rehabilitation center. High density lipoprotein cholesterol is a primary risk factor for cardiovascular disease with decreased levels associated with increased cardiovascular risk. The concentrations of HDLc observed in the SCI sedentary population were compared with 22 olympic caliber wheelchair athletes (SCI athletes) and 126 able-bodied controls. Total HDLc, HDL2, and HDL3 was significantly lower in the male SCI sedentary population (34.2 mg/dl, 8.9 mg/dl, 25.3 mg/dl) than the male SCI athletes (42.7 mg/dl, 13.9 mg/dl, 28.8 mg/dl) or male able-bodied control populations (47.1mg/dl, 11.3mg/dl, 35.8 mg/dl). A similar pattern emerged for the female subjects. The reduction in HDLc seen in the SCI sedentary would predict over a 60% increased risk of heart attack compared to nondisabled controls. The primary difference between the two SCI groups was the level of physical activity, suggesting that this may be an important parameter for elevating total HDLc and HDL2, and presumably decreasing the risk for coronary heart disease. Therefore, physical activity positively affects total HDL and the supposedly antiatherogenic subfraction HDL2 in the SCI patient.