Aim: The aim of this study was to evaluate the effect of radiotherapy on lipid peroxidation, total sulfhydryl groups (RSH) and nitric oxide (NOx) levels in plasma of cancer patients treated on different anatomic sites, and to compare the results with control subjects. Methods: 89 patients with various malignancies and 33 healthy control subjects were recruited for the study. Cancer patients were grouped according to the irradiation portals (head and neck, thoracic, breast, abdominal and pelvic). Two blood samples before and after the completion of the fifth week of radiotherapy were collected from each patient. Results: Plasma levels of malondialdehyde (MDA) and NO. of cancer patients before irradiation were found higher than those in control subjects. After irradiation, a marked lipid peroxidation increase was demonstrated as well as the significant decrease of plasma RSH level. Conclusion: The alterations of the parameters indicate enhanced oxidant stress and point to the necessity of antioxidant prophylaxis upon application of radiotherapy.