This study examined the relationship among regional and relative adipose tissue distribution, glucose, and lipid metabolism in men with spinal cord injury (SCI). After overnight fasting, 32 individuals with motor complete tetraplegia (Tetra) (n = 7) and paraplegia (Para) (n = 25) underwent resting energy expenditure and measurement of serum lipid profile, followed by an oral glucose tolerance test to measure plasma glucose and plasma insulin concentrations. Regional fat mass (FM) and fat-free mass were quantified using dual-energy X-ray absorptiometry. Relative adipose tissue was calculated as the ratio of leg FM/trunk FM, leg FM/whole-body FM, and trunk FM/whole-body FM. Individuals with Tetra have greater leg FM/trunk FM (45%) and leg FM/body FM (26%) and lower trunk FM/body FM (29%) ratios than individuals with Para (p < 0.05). Glucose area under the curve (AUC) was positively related to leg FM (r = 0.34, p = 0.05) but not to trunk or body FM. Strong negative relationships were noted between the ratio of trunk FM to body FM and glucose AUC (r = -0.38, p = 0.03) and low-density lipoprotein cholesterol (LDL-C) (r = -0.45, p = 0.001). Whole-body FM was negatively related to high-density lipoprotein cholesterol (r = -0.49, p = 0.007) after controlling for percentage of trunk FM. Both leg and trunk FM may play a pivotal role in determining the metabolic profile in individuals with SCI. Relative to whole-body FM and leg FM, trunk FM may induce a protective effect on glucose homeostasis and the LDL-C profile.