OBJECTIVE: To assess the effects of intravenous fish oil fat emulsion on the metabolic alterations induced by lipopolysaccharide (LPS) challenge in healthy volunteers. DESIGN: Two groups of eight healthy subjects were randomized to receive either two pharmacological doses of intravenous FO fat emulsion or no treatment. The FO group received twice 0.5 g/kg 10% emulsion (Omegaven) 48 and 24h before investigation. LPS (2 ng/kg) was injected as a bolus on the investigation day. Systemic parameters, indirect calorimetry, heart rate variability, and platelet membrane phospholipid composition were measured. RESULTS: Basal EPA and DHA content in platelet phospholipids was low (0.28% and 2.54%, respectively) and increased significantly after FO to 1.68% and 3.32%. LPS induced reproducible effects in all subjects. Fever was higher in the control [corrected] group than in FO group [corrected] the difference was significant from t (120) until t (360). FO blunted the neuroendocrine response: the rise in plasma norepinephrine was sevenfold lower at t (120) while the ACTH peak was fourfold lower. Tumor necrosis factor alpha was significantly lower between t (360) and t (180) in the FO group. CONCLUSIONS: Two doses of intravenous FO fat emulsion modified the phospholipid composition of platelets in healthy subjects. FO blunted fever and increased the neuroendocrine and the inflammatory responses to LPS.