The objective of the study was to quantify plasma myeloperoxidase (MPO) levels in systemic lupus erythematosus (SLE) patients and to evaluate a correlation between MPO levels and disease activity. 71 female SLE patients and 70 controls were studied. Patients were divided into two groups: Group I (n = 48) with SLEDAI-2K score 0-5 and Group II (n = 23) with SLEDAI-2K score > or = 6. Mann-Whitney test and Spearman rank correlation were used. Two-sided P values < 0.05 were considered significant and P values > or = 0.05 and < 0.08 were considered as a tendency. The median age of patients and controls were comparable and the mean disease duration was 99.2 +/- 61.7 months. MPO levels were higher in patients than controls [5.99 (4.38-8.64) vs. 5.00 (3.33-7.08) ng/ml, P = 0.02]. We did not find correlation between MPO levels and SLEDAI-2k (r = 0.07, P = 0.58). MPO levels were not affected by treatment with prednisone, cyclophosphamide or azathioprine, however, a tendency of lower levels was observed among patients under antimalarial drugs. There was no significant difference in MPO plasma levels between Group I and Group II (5.83 vs. 6.02 ng/ml, P = 0.99). MPO levels were higher in patients with arthritis than in those without arthritis (8.15 vs. 5.56 ng/ml, P = 0.010). No difference was observed among patients with and without other organs/systems involvement. SLE patients presented increased MPO plasma levels than healthy controls. Despite the lack of correlation between MPO plasma levels and disease activity, the higher MPO levels in patients with articular involvement suggests MPO may play a different role in the inflammatory process of some SLE manifestations.