Objective To investigate the relationship between serum fructose and uric acid levels in patients with polycystic ovary syndrome (PCOS). Design A case-control study. Setting University-affiliated in vitro fertilization clinic. Population 292 patients with PCOS and 482 controls. Main Outcome Measures Serum fructose, uric acid and metabolic measurements. Results Compared with controls, serum fructose and uric acid levels were significantly increased in women with PCOS and patients with PCOS accompanied by metabolic disorders exhibited higher serum fructose and uric acid levels (P < 0.001). Restricted cubic splines indicated that serum uric acid levels linearly and positively correlated with serum fructose levels in women with PCOS (Poverall < 0.001, Pnon-linear = 0.30), whereas no correlation was found in controls (Poverall = 0.712, Pnon-linear = 0.43). Additionally, even after adjusting for confounding factors, serum fructose levels were an independent risk factor for hyperuricemia in patients with PCOS (P = 0.001; odds ratio, 1.380; 95% confidence interval, 1.207–1.577). Conclusions There was a significantly positive association of elevated uric acid levels with serum fructose levels in PCOS and was closely correlated with PCOS-related metabolic disorders, highlighting the importance of further research into the biological mechanisms of fructose and uric acid in the development of PCOS. Funding National Natural Science Foundation of China (No. 82071607 and 32100691); LiaoNing Revitalization Talents Program (No. XLYC1907071); Fok Ying Tung Education Foundation (No. 151039); Key Research and Development Program of Liaoning Province (No. 2018225062); Outstanding Scientific Fund of Shengjing Hospital (No. 202003). Keywords Fructose; Uric acid; PCOS; Metabolic disorder