In this study, the comparative effects of half, normal and double clinical doses of artesunate; artesunate/sulfadoxine/pyrimethamine; artesunate/amodiaquine and their combinants [sulfadoxine/pyrimethamine and amodiaquine] on the semen parameters namely total sperm count, motility, morphology, debris and premature/primordial cell count of the male guinea-pig were investigated. The agents caused significant [P<0.05] decreases in total sperm count and sperm motility, with increases in abnormal sperm cells [morphology], debris and premature sperm cells. The effects were maximal at the subclinical doses and synergistic in the ACTs, compared to those of the individual partner agents. Artesunate, amodiaquine and artesunate/amodiaquine caused 54, 28 and 84% decreases in total sperm count, with 13, 31 and 64% decreases in sperm motility respectively. Conversely, the above drugs increased baseline morphology by 70, 30 and 264% respectively. Similar synergistic responses were obtained with artesunate/sufadoxine/pyrimethamine. These results may be explained in terms of the oxidative effects of these agents, through generation of free radicals, resulting in pathological damage to testicular structure/function.