This study is to investigate the effect of high serum uric acid (UA) level on oxidative stress and semen quality of male infertility patients.A cohort of 654 male individuals aged between 20 and 45 years old were included in this study, and their semen and venous blood samples were collected. The serum UA, blood glucose, blood lipids, and hormone levels were determined by chemiluminescence method. The changes in inflammatory factors, oxidative stress, adipokines, and biochemical indices in seminal plasma were determined by ELISA. Organic acids in seminal plasma were detected with reversed-phase ultra high performance liquid chromatography.Compared with the control group, the amount of semen and the total number of sperm in the hyperuricemia group significantly reduced (P < .05). Semen volume decreased with the increase of serum UA level, and the total number of sperm also decreased. The level of luteinizing hormone increased and the level of testosterone decreased in the hyperuricemia group. The concentration of superoxide dismutase decreased and the concentration of endothelin increased in the hyperuricemia group (P < .05). The concentration of seminal plasma α-glucosidase and alkaline phosphatase in the hyperuricemia group decreased significantly (P < .05). Compared with the control group, the contents of ascorbic acid, tartaric acid, lactic acid, and UA in the seminal plasma were significantly reduced in the hyperuricemia group (P < .05).Blood UA level may become a new risk predictor of semen quality in infertile men.