Correlation of plasma antioxidant enzyme activity with the course and outcome in first-episode schizophrenia patients (n=49) was analyzed in order to assess the possible utility of peripheral markers of oxidative stress as prognostic factors. These markers were measured shortly after the onset of schizophrenia, and again 1, 6 and 12 months later. A decrease in catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and glutathione (GSH) levels and total antioxidant status (TAS), as well as an increase in thiobarbituric acid reactive substances (TBARS), were observed 1 month after (p<0.05). 6-Months later, there was a reduction in TAS, GSH, SOD and GPx, and a increase in TBARS (p<0.05), with a normalization of CAT levels, indicating a persistent alteration of the antioxidant system and the maintenance of oxidative stress. At 12-months, a considerable decrease was observed in TBARS. Additionally, while the level of GPx decreased (p<0.05) further, SOD and GSH levels and TAS were normalizing, indicating a partial regeneration of the antioxidant defence system. These results indicate the possible contribution of oxidative stress to the onset and pathophysiology of schizophrenia, suggesting the involvement of an adaptive response in the antioxidant defence system in the course and outcome in first-episode schizophrenia patients.