In this study, we evaluated the effects of commonly used non-steroidal anti-inflammatory drugs (NSAIDs) on oxidative stress and anti-oxidant system. Sixteen healthy volunteers and 35 patients diagnosed as one of musculoskeletal disorders were included in the study. Patients were treated with one of the three NSAIDs (i.e. naproxen, tiaprofenic acid, acemetacin) or paracetamol for 15 days. Erythrocyte glutathione S-transferase, erythrocyte and plasma glutathione peroxidase, and erythrocyte catalase (CAT) activities and plasma malondialdehyde level as lipid peroxidation index were detected in the blood samples of the patients, at the beginning of the study (0 week), after treatment for 15 days (2nd week), and at the end of 1 week-washout period (3rd week). The most affected enzyme by NSAIDs was erythrocyte catalase, which tended to increase at the end of 2 weeks treatment, and decrease at the end of 1 week-washout period. In the groups treated with acemetacin, naproxen and tiaprofenic acid, plasma malondialdehyde levels were decreased at some extent, but at the end of washout period a rebound increase was observed in acemetacin group. Our results suggest that NSAIDs have different influences on oxidative stress and anti-oxidant system related parameters. These effects seem to be related with the mechanisms of some of the adverse effects, which are not well understood yet. Further studies with larger groups are needed to illuminate the relationship between adverse effects of NSAIDs and the effects of these drugs on anti-oxidant system, and to clarify their mechanisms of therapeutic action, as well.