Background: Neonatal sepsis is an important cause of morbidity and mortality despite the major advances in the management (Stoll, 2004). Objective: We aimed to evaluate the predictive value of alpha1-acid glycoprotein (alpha1AG) in the early diagnosis of neonatal sepsis. DESIGN: This case control study was conducted among newborn admitted to neonatal intensive care unit (NICU) of Sayed Galal University Hospital. Patient And Methods: A total of 90 newborn , 30 with confirmed sepsis by blood culture and laboratory investigation (Group I), 30 with clinically suspected sepsis (Group II), and 30 as a control group (Group III) were enrolled in the study. On admission to NICU, blood was taken for CRP, blood culture, and alpha1AG before starting antibiotic therapy. Results: We found that serum level of Alpha-1acid glycoprotein was highly significant between clinically suspected septic(Group II)  and control groups(Group III)  (p=0.00) and highly significant between confirmed septic(Group I)  and control groups(Group III)  (p=0.00).In the present study the sensitivity, specificity, positive and negative predictive values of alpha 1 acid glycoprotein at cut of value 136ng/ml were found to be 93%, 91.3%, 93.1%, 66.4%, respectively. Conclusion: Alpha-1-acid glycoprotein has high sensitivity and specificity in early diagnosis of neonatal sepsis.