Background: Neonatal sepsis (NS) is a major health problem throughout the world. The diagnosis of sepsis is challenging due to the non-specific nature of the clinical presentation, the variety of other neonatal disorders with the differential diagnostic workup, lack of sensitivity and specificity of available diagnostic procedures, and the delay in the results of blood cultures in addition to high negative results reported. The diagnosis of suspected sepsis has to be based on clinical symptoms together with biochemical parameters. A diagnostic marker with high diagnostic sensitivity and specificity would be a valuable tool for decreasing the burden of neonatal sepsis Purpose: Evaluate the validity of interleukin-6 (IL-6) in the early diagnosis of neonatal sepsis or the use of a combination of diagnostic markers, C-reactive protein (CRP), and IL-6. Methods: The study included 30 patients with NS (Group I) and 30 healthy newborns as control (Group II) were admitted to Neonatal Intensive Care Unit (NICU) from January 2017 to June 2017. All neonates were subjected to history taking, clinical examination, and laboratory investigations including complete blood count (CBC), blood culture and sensitivity testing, CRP, and IL-6. Results: the most causative organism of neonatal sepsis in NICU was Klebsiella spp. followed by CONS.  IL-6 results with cut-off value 50pg/ml, the sensitivity was 100%, the specificity was 90.32%, the positive predictive value of 90.63%, negative predictive value, and the diagnostic accuracy was 95.16. Moreover, IL-6 levels are significantly higher statistically in NS patients than controls. Conclusion: This study validated the diagnostic capability of IL-6 and showed that the combination of CRP and IL-6 as a panel for the early diagnosis of NS could enhance the sensitivity in the diagnosis of NS and may provide a new diagnostic strategy for NS patients Objective: Evaluate the validity of interleukin-6 (IL-6) in early diagnosis of neonatal sepsis or the use of combination of diagnostic markers, C-reactive protein (CRP) and IL-6. Patients and methods: The study included 30 patients with NS (Group I) and 30 apparently healthy newborns as control (Group II) were admitted to Neonatal Intensive Care Unit (NICU) from January 2017 to June 2017. All neonates were subjected to history taking, clinical examination, and laboratory investigations including: complete blood count (CBC), blood culture and sensitivity testing, CRP, and IL-6. Results: the most causative organism of neonatal sepsis in NICU was klebsiella spp. followed by CONS.  IL-6 results with cut-off value 50pg/ml, the sensitivity was 100%, the specificity was 90.32%, positive predictive value of 90.63%, negative predictive value, and the diagnostic accuracy was 95.16. Moreover, IL-6 levels are  significant  higher  statistically in NS patients than controls. Conclusion: This study validated the diagnostic capability of IL-6 and showed that the combination of CRP and IL-6 as a panel for the early diagnosis of NS could enhance the sensitivity in the diagnosis of NS and may provide a new diagnostic strategy for NS patients.