Introduction: Adipokines are differently regulated in the male reproductive tract and they were reported to affect sperm functionality. Serum omentin-1 was reported to have a range of effects on various cell types. Aim: To explore the presence of omentin-1in human semen, to investigate its relation with semen parameters in both fertile and infertile men and to compare its serum and seminal plasma levels in particular conditions such as; smoking, varicocele and leukocytospermia. Methods: Thirty nine infertile and 26 fertile men were enrolled in this case control study. They were subjected to history taking, clinical/physical examination, semen analysis, and measurement of omentin-1 in serum and seminal plasma, DNA fragmentation index (DFI) and seminal reactive oxygen species (ROS). Results: Omentin-1 was detected in all analyzed semen and serum samples (n=65). The concentration of omentin-1 was significantly higher in seminal plasma than in serum. Serum and seminal omentin-1 were positively correlated with sperm concentration and percentage of progressive motility and were negatively correlated with percentage of abnormal forms, DFI and ROS. The mean seminal plasma level of omentin-1 was significantly decreased in smokers and in patients with leukocytospermia. The mean serum level of omentin-1 was significantly decreased in patients with varicocele. Both serum and seminal omentin-1 levels were significantly lower in infertile patients than fertile men. Conclusions: Semen and serum Omentin-1 correlate with semen quality. In cases of leukocytospermia and smoking, seminal omentin-1 concentrations were decreased, suggesting that it may play a regulatory role in inflammation of the male reproductive system.