Background: Sepsis was found to increase the risk of mortality in children with multiple organ system failure (MOSF). The reported frequency of multiple organ dysfunctions in pediatric intensive care units (PICUs) varies .Hence there is a need for developing an objective measure of MOSF in PICU. Both pediatric logistic organ dysfunction (PELOD) score and pediatric risk of mortality (PRISM) were developed and validated for this purpose. Aims: To estimate epidemiology and outcome of variable sepsis syndromes and MOSF in critically ill children on day one admission to PICU ; and to estimate the diagnostic accuracy of PRISM III and PELOD scores in predicting outcome. Methods: Retrospective descriptive study including patients admitted to PICU of Cairo university hospital during the period from January (2011) to December (2011). Results: Out of 237 patients enrolled in our study; MOSF occurred in 72.2%, overall sepsis syndromes occurred in 77.2%; SIRS was found in 11.39%, sepsis 16.45%, severe sepsis 14.34%, isolated septic shock 2.5% and septic shock with MOSF 32.49%. Overall mortality was 39.4% (n=94). Mortality in patients with MOSF was 73.4% and in septic patients 67.02%. In both septic patients and patients with MOSF, independent risk factors for mortality were mechanical ventilation and neurological failure [O.R. 17.060, 3.55 and 35.62, 3.34, respectively]. In addition use of inotropes was a risk factor for mortality in septic patients [OR:3.8]. Prolonged length of stay (PLOS) > 7 days in patients with MOSF was 71.3% and 81.7% in septic patients. In both septic patients and patients with MOSF, independent risk factors for PLOS were mechanical ventilation, acute kidney injury and age ≤ 1 year [OR: 4.49, 2.97, 2.4 and 4.8, 3.3, 2.24, respectively]. Cardiovascular failure and use of inotropes were risk factors for PLOS in patients with MOSF [OR: 2.419, 2.688]. ROC analysis revealed that both PRISM III and PELOD scores had a good discriminating ability in predicting mortality [AUC: 0.726, p=0.00 and 0.79, p=0.00, respectively] but both were poor in predicting PLOS. Conclusions: Children with MOSF and septic patients presented on day one of PICU admission have higher mortality, and long PICU length of stay than those without. Both PRISM III and PELOD scores were good predictors of mortality.