Introduction: Hypermetabolism is universal in the severely burned and is characterized by catabolism of lean mass and body fat with associated insulin resistance. Adipokines are likely to play a role in these changes but have not been identified to date in burn patients. Methods: From a single burn ICU, 17 burn patients with an expected stay >14. days were studied. Study period began within 14. days of admission. Over 7. days, plasma samples were collected for measurement of leptin, adiponectin, resistin, ghrelin, insulin, and cortisol by ELISA. For comparison, samples from 15 healthy controls of similar age, BMI, and blood glucose were obtained. Results: Mean age was 33. ±. 17. years and BMI 26. ±. 3.4. Average burn size was 45. ±. 20% TBSA and ISS 32. ±. 10 with 72% having inhalation injury; in-hospital mortality was 29%. Estimated energy needs were 3626. ±. 710. kcal, of which 84. ±. 21% were met by enteral feeding with intensive insulin treatment (glucose 80-110. mg/ml). Using the homeostasis model assessment of insulin resistance, burned subjects were more resistant than controls (17. ±. 11.3 and 8. ±. 10.0). Insulin levels were elevated (57. ±. 35.6. μU/ml in burned subject vs. 26. ±. 31.1. μU/ml in controls), and cortisol concentrations increased (50. ±. 41.2. μg/dl vs. 12. ±. 3.9. μg/dl). These traditional hormone changes were associated with increased resistin (16.6. ±. 5.5. ng/ml vs. 3.8. ±. 0.9. ng/ml) and decreased leptin (8.8. ±. 8.9. ng/ml vs. 19.4. ±. 23.5. ng/ml), adiponectin (9. ±. 3.5. ng/ml vs. 17. ±. 10.2. ng/ml), and ghrelin (0.37. ±. 0.14. ng/ml vs.0.56. ±. 0.26. ng/ml). Conclusion: Patients with burns, who are characteristically hypermetabolic with hypercortisolism and insulin resistant, have significant changes in adipokine levels that appear independent of the magnitude of initial injury or metabolic derangement. In addition, suppression of ghrelin in the presence of decreased leptin and adiponectin levels in combination with increased insulin and resistin levels represent unexpected changes in the metabolic milieu of the injured patient possibly due to dramatic activation of inflammatory pathways, indicating strategies for treatment.