A group of 15 burned children and young adults with large burns (mean, 41% ± 15% BSA) were administered ibuprofen (40 mg/kg for 3 days). Each patient served as his or her own control in this crossover study (with and without ibuprofen). Paired calorimetric and temperature studies and urinary nitrogen measurements were performed. No nitrogen-sparing effect was identified for this dose of ibuprofen. However, patients demonstrated a statistically significant reduction in average rectal temperature (0.67°C) (p < 0.01) and in metabolic rate (11.4%) (p < 0.01) while taking ibuprofen. Linear regression analysis of the reduction in temperature versus the reduction in metabolic rate yielded a statistically significant correlation (p < 0.01) with a slope of 13.6% reduction in metabolic rate per degree centigrade reduction in the 72-hour average rectal temperature. These results support the hypothesis that ibuprofen attenuates the hypermetabolic response to thermal injury by blunting the temperature elevation that is usually seen.