The effect of administration of zinc and selenium on lipid peroxidation and endogenous antioxidant enzymes in albino rats was investigated. Forty-five (45) healthy rats were divided into nine (9) groups of five (5) rats each. Groups I, II, and III served as control; administered with normal chow and distilled water ad libitum, zinc gluconate and selenium and Trypanosoma brucei without treatment respectively. Groups IV, V, and VI were the pretreated infected groups that were administered with daily dose of 50mg per kilogram body weight of zinc, 10mg per kilogram body weight of selenium and combination of zinc and selenium respectively for seven (7) days. Whereas group VII, VIII and IX represented the post-infected treated groups that were administered with daily dose of 50mg per kilogram body weight of zinc, 10mg per kilogram body weight of selenium and combination of zinc and selenium respectively for seven (7) days. The control group of Trypanosoma brucei infected without treatment showed a significant (P<0.05) increase in the concentration of malondialdehyde (MDA), and decrease in superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities when compared with other control groups. Administration of zinc and selenium to the pre and post-infected groups caused significantly (P<0.05) lower values in the concentration of malondialdehyde (MDA), with significantly (P<0.05) higher activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in the liver and kidney. Treatment with zinc and selenium may contribute in protection against cellular damage during Trypanosoma brucei infection in rats.