Purpose: In this study, the aim was to determine the distinct effectiveness of serum amyloid A in the early stage of early-onset neonatal sepsis in premature infants. Methods: Preterm newborns hospitalised between 2014 and 2017 for suspected early-onset neonatal sepsis were included in this prospective study. Patients were evaluated according to clinical and laboratory findings at admission and at the 24th and 48th hours after admission. The serum amyloid A values of the patients with sepsis and a control group were compared, and the blood cultures were evaluated. Results: A total of 319 premature newborns were included in the study: 150 in the sepsis group and 169 in the control group. Their birth weight ranged between 590 g and 3000g and the gestational age was 24-36 weeks. The serum amyloid A values at admission were significantly higher in the cases diagnosed with sepsis compared to the control group. Conclusion: Serum amyloid A is a reliable diagnostic marker for the early onset of neonatal sepsis, and it has a higher sensitivity at symptom onset or in the first hours after birth in premature infants.