Amoxicillin/clavulanic acid has become one of the most widely prescribed antibiotics being advocated by WHO for treatment of infection. Its efficacy and potential to inhibit microorganisms had led to their increased use. There is the possibility that the drug may have potential toxic effects on humans following consumption. The present investigation was therefore undertaken to study the status of antioxidant defence system, oxidative stress and some biochemical indices following treatment with different combinations of amoxicillin/clavulanic acid (Augmentin® 375 and 625 tablets) treatments in rats. Thirty rats were divided into three groups: Group 1 (control) received no drug; Group II received Augmentin® 375 (14.25 mg/kg body weight), while, Group III received Augmentin® 625 (21.83 mg/kg body weight) twice for seven days. The result indicated that Augmentin® 375 and 625 induced marked renal and liver failure characterized by a significant increase (p<0.05) in plasma creatinine, urea, and bilirubin. Similarly, Augmentin® 375 and 625 significantly increased plasma total cholesterol by 29.4 and 38.1%, HDL- cholesterol by 53 and 83.5%, LDL- cholesterol by 36 and 96% and triglycerides by 18 and 26%, respectively when compared with control. Furthermore, plasma AST and ALT was significantly increased (p<0.05) by 27.7 and 42.6%, and 33 and 44.4%, respectively in the two treated groups when compared with control. Administration of Augmentin® 375 and 625 also caused significant decrease in hepatic reduced glutathione (GSH) and vitamin C by 35 and 61%, and 38 and 44%, respectively. Similarly, hepatic superoxide dismutase (SOD) and catalase activities decreased significantly by 33 and 56%, and 31 and 48.7%, respectively in the treated group. In addition, Augmentin® 375 and 625 significantly decreased the hepatic levels of glutathioneS-transferase (GST) by 44.7 and 53.4%, respectively. In conclusion, the result of the present investigation show that two different combinations of amoxicillin/clavulanic acid (Augmentin®375and 625) altered enzymatic and non-enzymatic antioxidant defence system and induced oxidative stress in rats. Key words: Amoxicillin/clavulanic acid, respiratory tract infection, antioxidant indices, oxidative stress, reactive oxygen species.