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Severe sepsis is not clinically apparent during the first 24 hours of hospitalization in most children with cancer and febrile neutropenia (FN), delaying targeted interventions that could impact mortality. The aim of this study was to prospectively evaluate biomarkers obtained within 24 hours of hospitalization as predictors of severe sepsis before it becomes clinically evident.Children with cancer, admitted with FN at high risk for an invasive bacterial infection in 6 public hospitals in Santiago, Chile, were monitored throughout their clinical course for occurrence of severe sepsis. Clinical, demographic and 6 biomarkers [eg, blood urea nitrogen, serum glucose, lactic dehydrogenase, serum C-reactive protein (CRP), interleukin (IL)-8, and procalcitonin] were obtained at the time of admission and after 24 hours. Biomarkers independently associated with severe sepsis diagnosed after the first 24 hours of hospitalization were identified by logistic regression analysis.A total of 601 high risk FN episodes were enrolled between June 2004 and October 2006; 151 (25%) developed severe sepsis of which 116 (77%) were not clinically apparent during the first 24 hours of hospitalization. Risk factors for severe sepsis were age ≥12 years [odds ratio (OR): 3.85; 95% confidence interval (CI): 2.41–6.15], admission CRP ≥90 mg/L (OR: 2.03; 95% CI: 1.32–3.14), admission IL-8 ≥200 pg/mL (OR: 2.39; 95% CI: 1.51–3.78), 24-hour CRP ≥100 mg/L (OR: 3.06; 95% CI: 1.94–4.85), and 24-hour IL-8 ≥300 pg/mL (OR: 3.13; 95% CI 1.92–5.08).Age ≥12 years and admission or 24-hour values of CRP ≥90/100 mg/L and IL-8 ≥200/300 pg/mL are predictors of sepsis not clinically apparent during the first 24 hours of hospitalization.