Objective: The effect of coadministering artesunate (ART), amodiaquine (AMO), and selenium were studied on mice induced with Plasmodium berghei.Methods: The study was conducted using 6 groups of 6 male mice each. Group A constitutes the negative control (unparasitized) while Group B represents the parasite control (parasitized) group. Mice in Groups C, D, E and F, respectively, received 2 mg/kg bw of ART, 6.12 mg/kg bw of AMO, combination of AMO and ART, and 0.945 mg/kg bw of selenium in addition to ART and AMO for 3 days. Thereafter, animals were anesthetized, and the organs were excised. Liver homogenate was prepared and used for analysis of for aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), total protein (TP), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and lipid peroxidation (malondialdehyde).Results: The results showed no significant alteration in AST and ALT, but ALP was significantly (p<0.05) increased in Group D. In addition, a significant drop (p<0.05) in GSH and SOD activities and significant (p<0.05) increase in TP was observed in group E. Histopathological studies revealed no degenerative change in the morphology of the hepatocytes of mice in Group F whereas Groups D and E showed mild inflammatory cells.Conclusion: Conclusively, the combination of ART-AMO therapy with selenium increases the efficacy and reduces potential toxicity of combined antimalarial drugs.