Abstract: Background: Despite increasing knowledge of pathophysiology and modern therapeutic approaches, the morbidity and mortality associated with early neonatal sepsis remains alarmingly high. Objective: To evaluate the effectiveness of serial C-Reactive Protein and its rising titer in comparison with complete blood count and blood culture as screening tool for diagnosing early neonatal sepsis in preterm. Methods: This study included fifty preterm neonates with clinical suspicion of early onset sepsis who admitted to the NCU of Al-Yarmouk Teaching Hospital in Baghdad. All were investigated at birth for CRP with titer and at 72 hours of life for second CRP. Complete blood count and blood culture also sent at 72 hours of life after notification to the changes in CRP titer and comparsion done between the results. Results: Early onset sepsis was found to be more common in males, very low birth weight and in very preterm infants. Confirmed sepsis with positive blood culture were 30% of studied preterm neonate .C-reactive protein sensitivity was 73%, specificity was 40% while accuracy showed 50% with no significant association between rising CRP, blood culture and CBC abnormalities in the current study. Conclusion: Rising CRP titer does have a role in the diagnosis of early neonatal sepsis in preterm but it is not specific enough to be the only indicator.