Background: Breast cancer is the most common cancer in Indian women. The aim of this study was to assess the levels of red blood cell (RBC) superoxide dismutase (r-SOD), RBC catalase (r-CAT), RBC glutathione peroxidase (r-GPx) and the ferric reducing ability of plasma (FRAP) in advanced breast cancer patients post mastectomy before and after chemotherapy. Methods: Female breast cancer patients between 27 and 65 years of age who were admitted to the Department of Surgery of the All India Institute of Medical Sciences in New Delhi were enrolled in the study. This study included two arms: a control group of healthy age-matched females (n=20) and patients undergoing treatment with a combination of the anticancer drugs cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) (n=55), No treatment was given to the control group. The CAF group received CAF treatment at weeks 0, 3, and 6, then surgery at week 9 followed by CAF treatment at weeks 12, 15, and 18. A three-week drug-free interval was included between each cycle of drug treatment. Blood samples were collected from control subjects and from patients in the CAF group before administration of drugs at week zero to establish a baseline, again weeks 12 and 18, and once more at the end of the 26-week treatment. Blood samples collected from the control subjects and CAF patients were analysed to determine levels of the endogenous antioxidants, r-SOD, r-CAT, r-GPx, and FRAP. Results: Levels of r-SOD, r-CAT, r-GPx, and FRAP in CAF-treated patients at 12, 18, and 26 weeks were significantly decreased (P<0.001) in comparison to the baseline levels observed at week zero. Conclusion: The results from the present study show that a change in the enzyme antioxidant systems in patients after chemotherapy and mastectomy causes an overall decrease in antioxidant levels. Chemotherapeutic agents induce oxidative stress that damages many cellular targets.