Associations between adipokines and bone mineral density (BMD) in knee osteoarthritis (OA) remain indistinct. The aim of this study was to investigate the cross-sectional associations between serum levels of adipokines and BMD in patients with knee OA. This study included 164 patients with symptomatic knee OA from the Anhui Osteoarthritis study. Serum levels of leptin, adiponectin, and resistin were measured using an enzyme-linked immunosorbent assay (ELISA). BMD at total body, spine, hip, and femur were measured by dual-energy X-ray absorptiometry (DXA). In multivariable analyses, serum levels of leptin were significantly associated with reduced BMD at total body, hip, total femur, femoral neck, and femoral shaft (β = − 0.019, 95% CI -0.034 to − 0.005; β = − 0.018, 95% CI -0.034 to − 0.003; β = − 0.018, 95% CI -0.034 to − 0.002; β = − 0.016, 95% CI -0.032 to 0.000; β = − 0.026, 95% CI -0.046 to − 0.006; respectively). Serum levels of adiponectin were significantly and negatively associated with BMD at total femur and femoral shaft (β = − 0.007, 95% CI -0.013 to 0.000; β = − 0.011, 95% CI -0.018 to − 0.003; respectively). However, no significant associations were found between serum levels of resistin and BMD at any site measured. Serum levels of leptin and adiponectin were significantly and negatively associated with BMD, suggesting potentially detrimental effects of leptin and adiponectin on BMD in knee OA patients.