Abstract: This research was designed to access the effect of chloroquine a common antimalarial and ascorbic acid a popular antioxidant, on oxidative stress and liver function in animal models, with the aim of applying the research findings to the treatment of some devastating tropical diseases. A total of forty mice comprising of twenty males and females were divided into four groups per sex category and test drugs were administered intra peritoneally (ip) in mono and combined doses to healthy mice. Chloroquine treatment increased all oxidative stress indices with catalase being significant (P<0.05) against control. Significant increases (P<0.05) were also indicated in superoxide dismutase (SOD) and in catalase activities in both sexes. Ascorbic acid generally reduced all (P>0.05) assayed stress indices but the reduction was significant (P<0.05) only in female mice as against control. A combined treatment of chloroquine and ascorbic acid did not show any significant decrease and increase in malondialdehyde (MDA) and SOD, but catalase increased (P<0.05). Increases (P<0.05) were observed in SOD and catalase activities in both male and female mice. The activities of liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined and confirmed using gamma glutamyl transferase (GGT) activity and increases (P<0.05) in the activity of this enzyme were observed in female mice given a combination treatment. This result indicates that ascorbic acid can ameliorate oxidative stress induced during normal aerobic metabolism in mice. Chloroquine and a combination of chloroquine and ascorbic acid treatment can adversely affect GGT in female mice.