Ovine malignant theileriosis is a fatal disease that is characterized by severe progressive anemia. In order to elucidate the underlying mechanisms involved in anemia, this study was designed to assess the antioxidant status and erythrocyte oxidative injuries in Iranian fat-tailed sheep that suffered from malignant theileriosis. The infected animals (infected group), composed of 50 Iranian sheep about 1-2 years old, naturally infected with Theileria sp., were divided into three subgroups according to parasitemia rates (<1%, 1-3%, 3-5%), and ten non-infected animals were also selected as the control group. Blood samples were taken and hematological parameters, the activities of antioxidant enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase, erythrocyte osmotic fragility, and serum concentrations of some trace elements (copper, iron, zinc, manganese, and selenium), were measured. As an index of lipid peroxidation, the level of malondialdehyde (MDA) was also determined. According to the results, a significant decrease in red blood cell (RBC) count, packed cell volume, the activities of SOD, GPX, and catalase (P <0.001), and also serum concentrations of Cu, Zn, Mn, and Se (P < 0.05) were evident in the infected sheep. In contrast, significantly increased levels of MDA and erythrocyte osmotic fragility (P < 0.001) as well as serum concentration of iron (P < 0.05) were recorded in the infected animals. The significant decrease in antioxidant enzyme activities and substantial elevated levels of lipid peroxidation and erythrocyte osmotic fragility associated with the increase in parasitemia indicate increased exposure of RBCs to oxidative damage. Also, it appears that disturbed antioxidant defense mechanisms can promote the development of anemia in ovine theileriosis.