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To assess the value of Presepsin and Pentraxin3 measurement in critically ill children.Prospective observational study conducted on 80 children admitted into Pediatric Intensive Care Unit (PICU) and 80 healthy controls. Patients were evaluated for presence of sepsis. Pediatric Risk of Mortality (PRISM) and Pediatric Index of Mortality (PIM2) were calculated. Serum Presepsin and Pentraxin3 were measured within 24 h of admission.Presepsin and Pentraxin3 were significantly higher among the whole patient cohort and among septic patients compared with controls (p < 0.001) but no difference was found between septic and non-septic patients. Pentraxin3, but not Presepsin, was significantly higher among non-survivors compared with survivors (p = 0.048) and was correlated with PIM2. Receiver operating characteristic (ROC) curve analysis revealed that Pentraxin3 had an AUC of 0.631 for prediction of mortality which was comparable to that of PRISM and PIM2. Presepsin was associated with a higher rate of mechanical ventilation and longer PICU stay.Presepsin and Pentraxin3 are acute phase proteins potentially useful for monitoring critically ill children and diagnosing sepsis. Pentraxin3 is associated with mortality but modestly discriminates survivors from non-survivors. Presepsin is associated with certain indicators of disease severity. Larger studies are certainly required.Presepsin and Pentraxin3 are acute phase proteins with potential use for management of critically ill children.Both markers are potentially useful for sepsis diagnosis.Pentraxin3 is associated with mortality but is not superior to PRISM or PIM2.Presepsin is associated with a higher rate of mechanical ventilation and longer PICU/hospital stays.