Objective: To evaluate the correlations between severity of illness scoring systems and biochemical markers of physiologic stress. Setting: Tertiary care pediatric ICU in a university hospital. Design: A prospective, clinical study. Patients: Twelve patients aged 2 to 120 months (four patients aged < 12 months) with varying diagnoses including sepsis, cardiovascular surgery, respiratory failure. Interventions: Oxygen consumption (Vo2), daily total urinary nitrogen, and the branch chain to aromatic amino acid ratio were correlated with the Physiologic Stability Index, Pediatric Risk of Mortality score, and Therapeutic Intervention Scoring System. Linear regression analysis and multivariate stepwise regression analysis were used to analyze the data. Measurements and Main Results: Pediatric Risk of Mortality score and Physiologic Stability Index correlated with Vo2 (r2 = .69, p < .001 and r2 = .52, p < .01, respectively) and with daily total urinary nitrogen excretion (r2 = .66, p < .001 and r2 = .62, p < .01, respectively). The Therapeutic Intervention Scoring System correlated with the total urinary nitrogen excretion (r2 = .69, p < .001) and branch chain to aromatic amino acid ratio (r2 = .49, p < .01). Correlations existed between Pediatric Risk of Mortality score and Physiologic Stability Index (r2 = .88, p < .001) and Pediatric Risk of Mortality score and Therapeutic Intervention Scoring System (r2 = .48, p < .01) Conclusions: The correlations were independent of diagnostic category, suggesting that the alterations in biochemical variables were most directly related to the overall severity of illness as measured by the scoring system.