Background: The optimal amount and type of fat in the nutrition support of burned patients have not been determined. The aim of this study was to test low-fat nutritional solutions, with or without fish oil, on protein metabolism, morbidity, and length of care in severely burned adults. Methods: In a prospective randomized clinical trial, 43 patients were assigned to one of the following groups: control (35% fat), low-fat solution (ie, 15% of total calories as fat), low-fat with fish oil, given for 30 days. Nitrogen balance, urinary 3-methylhistidine excretion, urinary cortisol, and clinical status were measured daily. Cortiosteroid-binding globulin and total and free serum cortisol were measured every 3 days. Results: Compared with controls, patients on low-fat support had fewer case of pneumonia: 3/24 us 7/13 (P =.02), better respiratory and nutrition status, and shorter time to healing: 1.2 vs 1.8 days% burned area (P = 0.01). There was no difference in nitrogen balance between groups, and 3-methylhistidine excretion was higher and serum free cortisol was lower in low-fat-fed patients than in controls. There was no difference between the two low-fat groups in any of the parameters measured. Conclusions: These study showed that low-fat nutrition support decreases infectious morbidity and shortens length of stay in burn patients. Fish oil does not seem to add clinical benefit to low-fat solutions. In addition, this study provides the first evidence that nutrition intervention modulates cortisol-binding globulin and the concentration of free circulating cortisol after a severe stress.