Metabolites of arachidonic acid, formed from omega-6 essential fatty acids (n-6), play a pathologic role in mortality from sepsis. Metabolites of eicosapentaenoic acid, formed from omega-3 essential fatty acids (n-3), are less potent inflammatory mediators. Dietary restriction of n-6 fatty acids or supplementation with n-3 fatty acids in the form of fish oil have been shown to decrease the production of n-6 metabolites. Male Sprague-Dawley rats (350-400 g) were divided to receive either rat chow (CHOW) or essential-fatty-acid-deficient chow (EFAD) and subdivided to receive 1 mL daily of either fish oil (N3), linoleic acid (N6), or normal saline (NS), via gastric gavage. Two weeks later, half of the animals in each group underwent cecal ligation and puncture (CLP) to induce peritonitis or sham (SHAM) celiotomy. Survival was tabulated for 7 days. Survival was significantly decreased for animals undergoing CLP for both the N6 and NS groups but not for the N3 group. Omega-3 fatty acids as the sole essential fatty acids or as a supplement to a "routine" diet, when fed to rats for 2 weeks before a septic challenge, improved survival in this peritonitis model.