The effects of phenytoin (PHT), levetiracetam (LEV) or their adjunctive treatment on the hypothalamic-pituitary-testicular axis in male Wistar rats were determined. Twenty-eight male rats (150-180 g) were randomised into four groups (N = 7). Groups I to IV received intraperitoneal treatment of either normal saline (0.2 ml i.p) or PHT (50 mg/kg i.p) or LEV (50 mg/kg) or PHT (25 mg/kg) and LEV (25 mg/kg) combination for 28 days. The organ weight, concentrations of reproductive hormones and semen profile were determined, while the brain, epididymis and testis were preserved in 10% neutral-buffered formalin for the histomorphological study. Data were analysed using descriptive and inferential statistics. The results were presented as mean ± SEM in graphs or tables, while the level of significance was taken at p < .05. The semen profile was altered significantly in all the treatment groups. The gonadotrophic releasing hormone, luteinising hormone and testosterone concentration decreased significantly in the PHT- and PHT + LEV-treated groups compared with control. There were various disruptions in the hypothalamus, pituitary and testis of the PHT- and PHT + LEV adjunctive-treated rats. In conclusion, chronic PHT + LEV treatment may pose deleterious effects on the hypothalamic-pituitary-testicular axis than single treatment of either of the two drugs in male rats.