Mice were divided into 3 groups: non-infected control, S. mansoni infected non-treated for 10 weeks and group receiving ozone intraperitoneally for 21 days 10 weeks postinfection. Results showed that ozone therapy in chronic schistosomiasis mansoni decreased worm burden, increased number of dead eggs, decreased both mature and immature eggs, increased RBC count, improved hemoglobin concentration with reduced reticulocytes %, as well as increased lymphocyte %, decreased neutrophil % and markedly increased eosinophil %. Platelet count was increased and bleeding time was markedly shortened, markers for hepatic function were improved, and malondialdehyde concentration decreased in liver and spleen but increased in intestine. Reduction of associated hepato-splenomegaly was noticed, with reduction in number and size of hepatic and intestinal granulomas, collagen area % and number of macrophages, with preservation of hepatic and intestinal histological profile in almost all areas. The results point to medical ozone as a promising agent to complement schistosomiasis mansoni specific treatment, helping to attenuate infection morbidity.