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Background: Leptin has an association with male infertility. However, only sporadic studies inconsistently reported the results. Aim and Objective. In this study, we aimed to perform a meta-analysis to investigate the relationship between leptin and male infertility., Methods: This study was performed based on published articles related to leptin and infertile males. PubMed, Web of Science, Google Scholar, Ovid + Cochrane Central Register of Controlled Trials, Wiley Online Library, Chinese CNKI, Chinese Chong Qing VIP, Chinese Wan Fang, and China Biology Medicine databases were searched to identify all relevant studies. All eligible works of literature were analyzed by the "meta" or "metan" command in STATA version 12.0 software. The standardized mean difference (SMD) of leptin concentration in serum or semen and 95% confidence intervals (CIs) were estimated for all studies. The heterogeneity was described with I 2 . The sources of heterogeneity were explored via metaregression, and stratified analyses, sensitivity analyses, and publication bias were performed., Results: Nineteen studies were included in the current meta-analysis, involving 1138 cases of infertile men and 756 controls. The SMD of leptin concentration in serum was 2.002 (95% CI: 1.086, 2.918), Z-test ( z ) z  = 4.29; p < 0.001, and I 2 was 97.3%, p < 0.001. The SMD of leptin concentration in semen was 3.274 (95% CI: 2.137, 4.411), z = 5.64; p < 0.001, and I 2 was 98.2%, p < 0.001. Notably, serum follicle-stimulating hormone (FSH) was slightly higher in infertile men (SMD = 3.695, z  = 2.33, p = 0.020, I 2  = 98.8%, p < 0.001). Other hormones, such as luteinizing hormone (LH) and testosterone, were also slightly higher, but the results were not statistically significant. In addition, sperm count (SMD = -4.533, 95% CI: -6.565, -2.501) and sperm motility (SMD = -7.894, 95% CI: -10.616, -5.172) inversely correlated with leptin levels in infertile males. Sperm abnormal forms did not show a statistically significant SMD of -0.076 (95% CI: -3.410, 3.258)., Conclusion: Leptin plays a potential role in association with male infertility. This study may effectively reveal the relationship between leptin together with other hormones and its association with male infertility. These results may also provide opinions on precautionary measures., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Yi Mo et al.)