Objectives: There are only a few earlier studies suggesting relationship between isotretinoin treatment and oxidative stress however, their results are conflicting. Therefore we aimed to concretize the influence of isotretinoin treatment on oxidant/antioxidant status together with paraoxonase-1 (PON1) activity for the first time. Methods: The study was performed on serum samples obtained from 35 acne vulgaris patients before and after three months of isotretinoin treatment. PON1 activity, total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI) and some routine biochemical parameters were monitored. Results: Dramatically decreased PON1 activity (p<0.001), increased TOS level and OSI value (p<0.001 and p<0.001; respectively) as well as slightly diminished TAC level were noted in posttreatment stage. Moreover significant increases were observed in lactate dehydrogenase and gamma glutamyl transpeptidase activities and levels of total cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, triglycerides, low density lipoprotein cholesterol/high density lipoprotein cholesterol ratio respectively (p<0.05, p<0.001, p<0.001, p<0.001, p<0.001, p<0.001 and p<0.001) while marked decrease was seen in high density lipoprotein cholesterol (p<0.01). Conclusion: This study revealed that decreased PON1 activity and increased oxidative stress may have a crucial role in the pathogenesis of isotretinoin's side effects. Further studies on a large number of patients are needed to verify these results.