Since neonatal infection remains a major cause of morbidity and mortality, several studies have searched for parameters that could be useful in early diagnosis of infection. The present study was performed to evaluate the usefulness of IL-8 as an accurate diagnostic tool for neonatal sepsis and to compare it with the simple at hand hematologic scoring system (HSS). The study included 41 neonates with clinical suspicion of sepsis admitted to the NICU of Kasr El-Aini and Abu El-Reish hospital. Another 20 normal neonates of matched gestational age. and weight were similarly studied serving as control group. Both groups were subjected to full history taking, thorough clinical examination and laboratory investigation including: CBC with differential count, CRP, blood culture and sensitivity and measurement of serum IL-8 by competitive enzyme immunoassay. Our study showed that HSS > 3 had a high specificity and predictive value of sepsis. IL-8 values were significantly higher in neonates with infection than those of the control (mean IL-8 was 1.6 + 1.3ng/ml versus 0.42 + 0.1ng/ml for patients and control groups respectively). The hematologic score & IL-8 levels were significantly higher in full term compared to the preterm infants.Our data suggest that assessment of serum IL-8 may be used as an early diagnostic tool with high sensitivity and specificity in neonates with suspicion of infection especially when combined with routine, simple at hand HSS and CRP.