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Patients after critical illness often remain undernourished due to reduced anabolic drive and diminished protein synthesis, in part due to post-admission energy restriction, and develop oxidative stress and tissue injury. Despite the harm of energy restriction, replacement of carbohydrate by fat has yielded mixed results. We hypothesized that the mixed feeding regime would increase oxidative stress and clinical outcome, but would not improve protein anabolism or muscle bulk. Fifty-three patients after elective surgery were randomized to either be fed according to a standard feeding guideline (CHO, n=22) or to be fed according to the diet that restored carbohydrate (fat-CHO, n=31). Body composition, muscle strength, and inflammatory status were assessed during the first three days and six months after admission. Glucose oxidation rates were determined over the first week, and protein turnover rates were determined over the first month. Muscle biopsies were analyzed for markers of inflammation, oxidative stress, and muscle mass. There was no significant difference in rates of lean tissue accretion between the groups, but a trend toward greater muscle strength in fat-CHO was observed, and fat mass was lower at the end of the study. Oxidative stress was decreased during the first day in the fat-CHO group, and inflammation did not differ between groups. Muscle mass was higher in the fat-CHO group and correlated with muscle strength. In conclusion, feeding according to the formula that replaced carbohydrate by fat did not affect lean tissue accretion, but demonstrated an improved carbohydrate metabolism