Background: Leptin has been reported to have positive effects on cognition but has not been studied in a population-based sample or stratified by race or gender. Methods: Leptin and fat mass were measured in 2,731 subjects, including 50% African Americans. Eight years later, subjects were administered the Montreal Cognitive Assessment (MoCA). Demographic factors and baseline measures, including a deficiency in leptin or levels in excess of what was predicted by fat, were investigated to see which predicted cognitive performance. Results: There was a statistical trend for lower leptin levels to be associated with higher cognitive scores. Once stratified by race and gender, excessive leptin was associated with lower MoCA total scores and delayed recall domain score for black men, but white men demonstrated a reverse relationship. Conclusion: Excess leptin appears to have differential effects on delayed recall in black and white men.