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Background: Increased dietary consumption of the n-3 polyunsaturated fatty acids (PUFA) eicosapetaenoic acid (20: 5n-3; EPA) and docosahexaenoic acid (22: 6n-6; DHA) is associated with their incorporation into circulating phospholipid and increased production of lipid peroxide metabolites. The relationship between peripheral blood mononuclear cell (PBMC) function, n-3 PUFA intake and antioxidant co-supplementation is poorly defined in rheumatoid arthritis (RA) patients. This study was designed to evaluate tumor necrosis factor-α (TNF-α) and interleukin (IL) 6 production by PBMC in RA. Methods: Fifty-five patients (50 female, 5 male; mean age = 47 ± 11 years) were investigated in three groups in a randomized double-blind clinical trial. Patients were randomly assigned to one of these three groups: group 1 (G1) was received placebo (MCT oil, 2 g/d plus vitamin E placebo), the second group (G2) was received n-3 fatty acids (1.2 g/d; EPA/DHA plus vitamin E placebo), and the third group (G3) was received n-3 fatty acids (1.2 g/d; EPA/DHA) plus 100 IU/d vitamin E. Medication dose was intact during the study. Data were compared between groups using analysis of variance (ANOVA). Findings: Fish oil n-3 fatty acids supplementation of diet decreased production of TNF-α (P = 0.007) by stimulated PBMC in G2 and G3 in relation to G1. Also G3 in relation to G2 and G1 showed significant decrease with respect to malonaldehyde (MDA) (P = 0.005). Conclusions: Consumption of omega-3 fatty acids with vitamin E not only decreased production of inflammatory parameters but also decreased lipid per-oxidation in RA patients. Key words: Rheumatoid arthritis, PBMC, N-3 fatty acids, Vitamin E.