AB - CONTEXT: Hyperglycemia and insulin resistance are common findings in critically ill patients and associated with increased morbidity and mortality. OBJECTIVES: To investigate the hyperglycemic response to critical illness in children. DESIGN: Observational cohort study. SETTING: University affiliated pediatric intensive care unit. PATIENTS: Six children with meningococcal sepsis (MS), ten children with meningococcal septic shock (MSS). MAIN OUTCOME MEASURES: Differences in blood glucose levels (measured during 72 h after admission) and differences in plasma levels of glucoregulatory hormones (insulin, GH, IGF-1, cortisol, glucagons, leptin), soluble cytokine receptors (sTNF-R55, R75, sIL-1-R2) and IL-6 on day 3 between MS and MSS patients. RESULTS: Blood glucose levels on day 2 and 3 were higher in MSS patients than in MS patients (7.5 (3.9-13.0) vs. 5.1 (4.0-6.0) and 6.5 (4.0-9.9) vs. 5.5 (4.8-6.8) mmol/l, both P < 0.05). Maximum blood glucose values recorded in individual patients were higher in MSS patients (9.3 (6.5-13) vs. 7.2 (6.2-9.9, P < 0.05) and correlated with severity of illness (r = 0.833, P < 0.001). Insulin levels in MSS patients were significantly lower (7.2 vs. 19.0 mU/l, P < 0.001) compatible with insufficient insulin response to hyperglycemia while MS patients showed insulin resistance. Insulin levels correlated inversely with levels of sTNF-R55 and R75 (r = -0.814 and -0.878, both P < 0.001) suggesting suppression of the pro-inflammatory response on insulin secretion. CONCLUSION: Hyperglycemia associated with hypoinsulinemia rather than insulin resistance may be the normal pathophysiological response in acute meningococcal septic shock in children. Our study emphasizes that application of intensive insulin therapy in critically ill children demands further investigation.