Objective-In this prospective study, we aimed to determine the efficacy of doxycycline and doxycycline plus ceftriaxone for the treatment of asymptomatic men with leukocytospermia. Method-Seventy men were included in this randomized and placebo-controlled study. White blood cell (WBC) concentrations were determined by peroxidase assay during the routine semen analysis. Twenty-four of 70 men with leukocytospermia were randomized as control group and administered placebo (group I), 25 received doxycycline alone (group II), and 21, doxycycline plus ceftriaxone (group III). Doxycycline, 100 mg, was given twice a day for ten days and ceftriaxone, 1 g, in two doses for only one day. After the treatment, semen analyses were repeated. Results-After the treatment there was a significant decrease in WBC counts in groups II and II when compared with group I (P < .05). Both antibiotic regimens were found to be equally effective. However, the time needed for resolution of leukocytospermia (similar to 4 weeks) was similar between the control and treatment groups. Conclusion-Although both antibiotic regimens significantly, and equally improved the white blood cell counts in men with leukocytospermia, they failed to treat the leukocytospermia, i.e., to bring the count below the limit of one million WBC/mL. Therefore, it is doubtful that antibiotic therapy should be recommended for asymptomatic men with leukocytospermia.