Breast cancer (BC) is one of the most frequently observed malignancy in females worldwide. Today, tamoxifen (TAM) is considered as the highly effective therapy for treatment of breast tumors. Oxidative stress has implicated strongly in the pathophysiology of malignancies. This study aimed to investigate the changes in the levels of oxidants and antioxidants in patients with newly diagnosed and TAM-treated BC. Sixty newly diagnosed and 60 TAM-treated women with BC and 50 healthy volunteers were included in this study. Parameters including total oxidant capacity (TOC), total antioxidant capacity (TAC), and catalase (CAT) activity were determined before and after treatment with TAM. The serum levels of TOC and oxidative stress index (OSI) were elevated significantly (P<0.001) in newly diagnosed BC patients compared with control, while the level of TAC and CAT activity were observed to be statistically declined (P<0.001). Furthermore, the BC patients on TAM treatment have shown highly significant levels of serum TOC (P<0.05) and TAC (P<0.001) with a significant reduction (P<0.001) in CAT activity compared with control. In TAM-treated patients compared with newly diagnosed BC patients, the TOC level was decreased, the TAC level was increased, the OSI level was decreased and the CAT activity was decreased. The results indicate a strong and aggressive association between oxidative stress and the first onset of BC, as well as the tendency of TAM drug to improve the levels of TOC, TAC, and OSI in BC patients, but it had a reduction influence on CAT activity.