Body weight is known to be associated with bone mass, however, it is unclear whether body composition, as reflected by the percent of total weight that is fat tissue (%fat), is associated with bone mass independently of weight. Fat tissue is metabolically active, and hormonal factors may mediate an association of %fat with bone mass. Leptin, a hormone produced in fat tissue, has recently been shown to be inversely related to bone mass in mice, but whether it is related to human bone mass is uncertain. We sought to investigate the associations of %fat and of serum leptin concentration with bone mineral density (BMD) in a cohort of 153 premenopausal women. BMD measurements of the total hip, lumbar spine and total body as well as body composition were measured by dual energy X-ray absorptiometry (DXA). Serum leptin levels were established using a commercial competitive binding assay. Individually, body weight, %fat and leptin were each positively associated with BMD at all three sites. However, when we examined BMD either as a function of both body weight and %fat together, or as a function of both body weight and leptin together, we found that for a given body weight, BMD appeared to be inversely associated with %fat and similarly appeared to be inversely associated with leptin. When BMD was examined as a function of %fat and leptin together, we found that for a given %fat, leptin appeared to be inversely associated with BMD. In summary, the results of this study suggest that for a given body weight, a higher proportion of fat and a higher serum leptin concentration have negative associations with bone mass in premenopausal women.