Background: Infertility is a common social and health problem. Male factor is a major cause in 30% of infertile couples. Smoking is common at reproductive age and its effect on fertilitiy is still in controversy. Studying its effect on fertility helps in the management of infertility. Objectives: To assess the effect of smoking on serum sex steroidal hormones as well as on seminal plasma (SP) IL-2, IL-6 and conventional semen parameters in infertile men and their correlations between each other. Methods: Seventy male partners of infertile couples (30 smokers and 40 non-smokers) were involved in this study. The man was considered smoker if he had history of smoking of more than 10 cigarettes per day for at least one year. Semen analysis was done according to world health organization (WHO) 2010. Specific kits were used for measurement of serum testosterone, serum estradiol II, SP IL-2, and SP IL-6. Results: The median of SP IL-2 was significantly (p<0.05) higher in smokers than in non-smokers group and positively correlated with SP IL-6 in them. In addition, IL-2 was negatively correlated with semen volume, sperm motility and morphology, while IL-6 was negatively correlated only with sperm motility. However, there was no significant difference of serum sex hormones level or on semen parameters between smokers and non-smokers. Conclusion: Cigarette smoking affect cytokine levels in the seminal plasma but has no effect on serum sex hormones level or semen parameters.