Background: Leptin is an adipocyte —secreted protein that participates in the regulation of energy homeostasis. It prevents the body from storing fat, controls hunger and cravings, regulates food intake and energy expenditure, provides the body with an index of nutritional status and controls the whole body fat metabolism. Leptin is a product of ob gene created by adipocytes. It seems to signal metabolic information to the reproductive system. Objective: The aim of this study to evaluate the relationship between serum leptin and infertility in oligozoospermic men. Materials and Methods: Seventy men were investigated; fertile normozoospermic as a control (n=35) and infertile oligozoospermic (n=35). The patients underwent estimation of body weight (kg), height body mass index (BMI), semen analysis, serum FSH, LH, testosterone and leptin, lipid profile and serum malondialdehyde (MDA). The infertile group was given a treatment course of clomiphene citrate (50 mg) and vitamin E (400mg) and then all the previous parameters were reevaluated after 3 months. Results: Mean body weight was significantly higher in infertile oligozoospermia compared to controls. The height showed no significant difference between the groups. Hormonal profile revealed significant (P=0.0001) difference in FSH between control group and oligozoospermic group (7.04±4.20 versus 3.35±1.47 mIU/ml), but after treatment with clomiphene citrate and vitamin E there is a slight non-significant (P=0.231) decrease in the level of FSH in oligozoospermic group. The level of testosterone showed a statistically significant (P=0.0001) difference between fertile normozoospermic (5.52 ±1.29 ng/ml) and infertile oligozoospermic. This hormone showed a significant (P<0.0001) increase in its level after treatment with clomiphene citrate and vitamin E (3.48±1.56 ng/ml). Other hormone showed non significant difference between the two groups pre and post treatment. Lipid profile showed no significant difference between the two groups. There was no significant (P=0.477) difference in serum MDA between the control and the infertile groups (4.69±1.32 vs. 5.18±1.19 µmol/L) respectively, but after treatment the results showed a mild significant (P=0.026) decrease in comparison to the level in the control group and also a significant (P=0.0001) decrease in comparison to the level before treatment. Infertile oligozoospermic had significantly higher serum leptin level (8.03±1.22 ng/ml) than control (3.62 ± 1.00 ng/ml). Conclusion: Serum leptin demonstrated a significant positive correlation with age, body weight, BMI and a significant inverse correlation with serum testosterone. It had nonsignificant correlation with the height and sperm concentration. These results are suggestive of a link between the adipocyte derived hormone leptin and male reproduction.