Abstract: Malignant ovine theileriosis is a fatal disease of sheep caused by Theileria hirci. The present study was designed to estimate the levels of plasma Homocysteine (Hcy), antioxidant enzymes, antioxidant vitamins and lipid peroxidation of erythrocytes and also to evaluate their correlations in different parasitemia rates in naturally infected sheep. Fifty Iranian sheep, about 1-2 years old, naturally infected with T. hirci were selected and divided into 2 subgroups according to their parasitemia rates (<2%, 2-4%). Ten non-infected animals were also selected as controls. Blood samples were collected and Hcy, antioxidant enzymes, antioxidant vitamins and lipid peroxidation of erythrocytes were measured. Our results showed that the activities of erythrocytic antioxidant enzymes including SOD, GPX and catalase were substantially reduced in infected sheep. Furthermore, the animals with higher parasitemia rate showed remarkable declines in SOD, GPX and catalase activities. There was a significant rise in the level of MDA, particularly in the animals with the higher (2-4%) parasitemia rates. In addition, it was evident that coinciding with the elevation of the parasite-bearing erythrocytes in infected animals, the level of lipid peroxidation in RBC membrane was significantly increased. Although the concentration of vitamin C showed a significant decrease in infected sheep with <2% parasitemia rate, the concentrations of antioxidant vitamins (A and E) generally showed no remarkable alterations. In our study, a significant increase was evident in the level of homocysteine in sheep suffering from theileriosis. Our data also showed that the increase in of parasitemia was coupled with the elevation of homocysteine level (r = 0.34, p<0.05).