Background: Neonatal sepsis is defined as a clinical syndrome of bacteremia with systemic signs and symptoms of infection in the first 4 weeks of life. Alpha-1 acid glycoprotein is one of the lipocalin family and members of acute-phase protein; it appears to function in modulating the activity of the immune system during the acute phase reaction. Objective: This study aimed to assess α-1AGP as a marker in the diagnosis of EOS.  Patients and Methods: This study was a prospective case-control study conducted on full-term neonates up to 7 days of life, admitted to the neonatal intensive care unit of Zagazig University Hospitals. The studied neonates were divided into 3 groups first confirmed cases (20) of early-onset sepsis, confirmed clinically and with a positive blood culture. Second suspected cases (20), with clinical features of sepsis and non-specific lab markers. Third group control (20), are apparently healthy term newborns, delivered in the Zagazig University Hospital. Alpha-1 acid glycoprotein was measured for all neonates. Results: There was a statistically significant difference among the studied groups as regard alpha one acid glycoprotein. It is a good diagnostic marker detection of cases. Conclusion: Alpha-1-acid glycoprotein appeared to be a useful marker for the early detection and diagnosis of early-onset neonatal sepsis.