Abstract: The effect of antioxidative agents, Nigella sativa oil and melatonin, in protection against the oxidative processes induced by schistosomiasis was studied on haematological parameters, granuloma formation and tissue reaction of liver, intestine and kidney of mice experimentally infected with Schistosoma mansoni. N. sativa oil (1.14 g kg-1 orally) or melatonin (3.55 mg kg-1 i.p.) was administrated daily for 30 days starting from 1st day of infection. Haematological results revealed that treatment with melatonin and N. Sativa oil caused significant decrease in total leukocyte count while, RBCs, Hb content and PCV were increased significantly with N. sativa- treatment as compared with infected and melatonin-treated group. Morphometeric and histopathological findings of liver revealed a modulation in the pathological profile of schistosomiasis by reducing the severity of histopathological changes and attenuating hepatic granuloma. N. sativa oil did not interfere on the granuloma evolution in intestine, although, melatonin markedly reduced the fibrotic areas. Also, these antioxidants markedly ameliorated most of the pathological changes occurred in kidney. The effects of the antioxidants may be attributed partly to their early administration before the stimulation of the immune system or due to a modulation in the immune response in general.