Objective To assess whether variables reflective of early metabolic responses to injury are predictors of outcome in critically ill trauma patients. Design Clinical inception cohort study comparing conventional measures of injury severity with early host response markers for the correlation of each with outcome. These data are prospectively collected in a group of patients being evaluated in a nutritional support investigation. Setting Intensive care unit (ICU) of a major Level I trauma center. Patients Seventeen blunt trauma patients, aged 18 to 60 yrs with an Injury Severity Score of 2:15, requiring early mechanical ventilation. Interventions Blood and urine samples were routinely obtained from patients undergoing nutritional support by one of three routes. Measurements and Main Results Conventional assessment was consistent with moderate severity and variation: Injury Severity Score, 41 pL 15; Glasgow Coma Score, 11 pL 4; admission circulating lactate concentration, 4.8 pL 2.2 mmol/L; and first 24-hr transfusion requirement, 3.1 pL 2.9 L. The mean concentrations of inflammatory marker during the first week were: cholesterol, 2.67 pL 0.80 mmol/L (103.2 pL 31 mg/dL); C-reactive protein, 23 pL 11 mg/dL; transferrin, 1.44 pL 0.47 g/L; glucose, 9.21 pL 2.27 mmol/L (166 pL 41 mg/dL); albumin, 26 pL 5 g/L; and nitrogen loss, 24 pL 9 g/d. Hospital outcome variables were: ventilator days, 17 pL 7; ICU days, 26 pL 10; hospital days, 38 pL 15; occurrence rate of adult respiratory distress syndrome (ARDS), 35%; infections, 82%; multiple organ failure, 71%; and total of hospital plus professional charges, 125,000 pL 56,000. A significant (p < .05), but weak, correlation existed between all seven outcome variables and the inflammatory markers: ventilator days with cholesterol and C-reactive protein; ICU days with transferrin; total stay with cholesterol; ARDS with C-reactive protein; infections with glucose, cholesterol, and nitrogen loss; multiple organ failure with albumin and C-reactive protein; and financial charges with glucose. However, a significant correlation existed between only two of seven outcome variables and conventional measures of severity: multiple organ failure with lactate and financial charges with transfusion requirement. Conclusion Readily obtainable inflammatory marker measurements may better reflect the summation effects of the early perfusion deficit and tissue injury in the blunt trauma patient compared with conventional measures of injury severity. (Crit Care Med 1994; 22:667–672)