Background: Neonatal sepsis (NS) is one of the leading causes of morbidity and mortality both among term and pre term infants. Early diagnosis of NS is difficult because of non specific signs and symptoms and non infectious disease may mimic NS. Rapid diagnosis of bacterial infections is crucial for early initiation of adequate antibiotic treatment. Systemic inflammation and sepsis lead to an increased release of Pro-Adrenomedullin (pro- ADM) into circulation thus it could be helpful in the early diagnosis of sepsis and in monitoring such conditions. Objective: To determine serum levels of pro-ADM in newborns with sepsis and its relation to diagnosis and prognosis. Methodology: Our study included fifty neonates fulfilled the criteria of sepsis (group1), they were subclassified into 2 subgroups; 29 cases with proven sepsis who had positive blood cultures (group1a) and 21 cases with clinical sepsis who had negative blood cultures (group1b), forty healthy gestational age, birth weight and sex matched neonates served as a control (group 2). Serum levels of Pro-ADM were measured by ELISA in all neonates and blood cultures were done in septic ones. Results: Serum level of Pro-ADM was significantly higher in group1as compared with group 2 (P=0.000) and in group1a as compared with group1b (P < 0.001). There was highly significant increase in serum level of pro-ADM with increased severity of NS (P = 0.000) and in non- survived neonates compared to those who survived (P = 0.000). Serum levels of Pro-ADM were positively correlated with WBCs count, I/T ratio (immature-to-total neutrophil ratio) and CRP serum level (r = 0.361, P = 0.010, r = 0.320, P = 0.024, r = 0.343, P = 0.015) respectively. Conclusions: Pro-ADM can be considered as valuable biomarker for diagnosis and prognosis of NS.