Coffee has been proposed to have benefits for chronic diseases; however, the relevant mechanism remains to be elucidated. We conducted a cross-sectional study and evaluated the levels of adiponectin and leptin in relation to coffee consumption. We included a total of 4406 individuals (men = 2587 and women = 1819) for adiponectin analysis and 2922 individuals (men = 1731 and women = 1191) for leptin analysis. Participants answered number of cups of coffee per week and types of coffee they consumed and their serum levels of adiponectin and leptin were measured using an enzyme-linked immunosorbent assay. We found that increasing coffee consumption was associated with increased levels of adiponectin among women; geometric means of adiponectin were 8.0 (95% CI: 7.2-8.9 μg/mL) among women who regularly consumed 15 or greater cups/week, but 7.5 (95% CI: 6.8-8.4 μg/mL) among women who did not consume coffee (P for trend = .009). Leptin levels were inversely associated with coffee consumption among both men and women (P for trend = .04 for men and 0.04 for women); geometric means of 15 or greater cups of coffee per week were 2.6 (95% CI: 2.4-2.8 ng/mL) among men and 5.1 (95% CI: 4.5-5.8 ng/mL) among women, but for noncoffee drinkers, geometric means were 3.0 (95% CI: 2.7-3.3 ng/mL) for men and 5.8 (95% CI: 5.1-6.6 ng/mL) for women. Coffee consumption was associated with higher circulating levels of adiponectin and lower circulating levels of leptin. Our study may suggest that improvement in adipocyte function contributes to the beneficial metabolic effects of coffee consumption.