The incidence of allergic diseases has increased, and a relation between allergy and dietary fatty acids has been proposed. Modulation of the maternal immune function during pregnancy may have an impact on future clinical outcomes in the child. The aim of this study was to determine the effects of omega (omega)-3 long-chain polyunsaturated fatty acids (LCPUFA) supplementation during pregnancy on the plasma fatty acid composition in relation to the maternal immune function. Pregnant women with allergic disease in their immediate family were supplemented daily with 2.7 g omega-3 LCPUFA (n = 70) or 2.8 g soybean oil as placebo (n = 75) from the 25th gestational week. The proportions of eicosapentaenoic acid and docosahexaenoic acid in plasma/serum phospholipids increased in the omega-3-supplemented group, whereas arachidonic acid decreased during intervention. Lipopolysaccharide-induced prostaglandin E2 secretion from whole blood culture supernatants (n = 59) decreased in a majority of the omega-3-supplemented mothers (18 of 28, p = 0.002). The decreased prostaglandin E2 production was more pronounced among nonatopic than atopic mothers. The lipopolysaccharide-induced cytokine and chemokine secretion was not affected. Our results indicate that omega-3 LCPUFA supplementation during the last trimester may dampen certain immune responses involved in allergic inflammation.