Background: Crohn disease (CD) is associated with osteoporosis and other extraintestinal manifestations that might be mediated by cytokines from circulating (peripheral blood) mononuclear cells (PBMCs). Fish oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduces disease activity in patients with CD with raised laboratory markers of inflammation and in healthy subjects alters PBMC function. Objective: We investigated the effect of fish oil plus antioxidants on cytokine production by PBMCs from patients with CD with raised C-reactive protein concentrations (≥6.9 mg/L) or erythrocyte sedimentation rates (≥18 mm/h). Design: A randomized placebo-controlled trial of fish oil (2.7 g EPA and DHA/d; n = 31) or placebo (olive oil; n = 31) for 24 wk was conducted in patients with CD. The fish-oil group additionally received an antioxidant preparation (vitamins A, C, and E and selenium). Exclusion criteria included corticosteroid use. Fatty acid composition was measured by gas chromatography. Production of tumor necrosis factor α, interferon γ (IFN-γ), and prostaglandin E2 (PGE2) was measured by enzyme-linked immunosorbent assays after stimulation with mitogen and endotoxin (lipopolysaccharide). Results: Fish-oil plus antioxidant dietary supplementation was associated with higher EPA and DHA incorporation into PBMCs (P