The purpose of the study was identification of additional differential diagnostic markers of urethritis in men by analyzing local and systemic status. Methods. We analyzed the indicators of local and systemic cytokine status in men with chronic urethritis (40 men with chronic viral urethritis and 40 men with viral and bacterial urethritis). The comparison group (control group) consisted of 20 healthy male volunteers. Cytokines were determined by ELISA, semen analysis indicators according to WHO protocol (5th ed., 2010). Results. In chronic viral urethritis diagnostically significant is the improvement of TNFa in the venous blood serum, as well as a marked reduction of index IFNy/IL10 in the venous blood serum and seminal fluid, suggesting a dysregulation of the immune response at a local and systemic level in such patients. With mixed urethritis of viral-bacterial etiology diagnostically significant was the authentic increase in TNFa levels in the ejaculate that was significantly higher compared to the group of men with herpetic urethritis and control group, combined with strong content of the same cytokine in the venous blood serum, which indicates a high apoptotic activity precisely in this investigated group and helps to maintain chronic inflammation and impaired fertility. Conclusions. The increase in TNFa levels higher than 21 pg/ml in the venous blood serum and 12.4 pg/ml in the ejaculate is an additional criterion for the diagnosis of chronic viral-bacterial urethritis. TFNß levels in the ejaculate exceeded the values of both control group and group with viral urethritis, indicating that the negative impact of herpes infection on the clinical course of urethritis of mixed etiology and affects adversely on the reproductive health of men.