Background: Despite the improvement in neonatal care, late onset sepsis (LOS) remains an important issue in neonates admitted to Neonatal Intensive Care Unit (NICU) and have been thought to be one of the main causes of morbidity and mortality especially in preterm ones Objective: The aim of this work was to assess the clinical usefulness of serum endocan as an indicator of late onset sepsis (LOS) in preterm neonates. Study Design: We carried out this prospective cross sectional study on111 preterm neonates; 61 treated for LOS and 50 control preterm neonates without sepsis. Sepsis group was further subdivided to proven and suspected sepsis groups according to positive blood culture. CBC, with differential count including immature by total ratio (I/T ratio), CRP, IL-6, and serum endocan were done to all preterm neonates within the first 2 hours of sepsis suspicion and at 3days and 7days later. Results:  Sepsis group showed significantly higher I/T ratio, CRP, IL-6, and serum endocan than control group (p < 0.01). Serum endocan was higher in preterm neonates with proven sepsis than suspected ones (p=0.04); also increased at the 3^rd day of onset of the sepsis then decreased at the 7^th day of onset (p < 0.01 for both). There were significant positive correlations between serum endocan and both CRP and IL-6 (p < 0.01). ROC curve analysis showed that endocan at a cut-off point of >5.5 ng/ml showed 88% sensitivity and 85 % specificity with 87% negative and positive predictive values. Conclusions: Serum endocan was higher in septic than non-septic preterm neonates; which may indicate the usefulness of endocan as a marker of LOS not only in the early diagnosis but also as a follow up of treatment in those neonates