Objective: Apelin is a proinflammatory adipocyte-derived factor. The aim of this study was to evaluate the role and significance of serum apelin as a new sepsis marker in the identification of full-term and preterm new-born infants with early-onset sepsis. Material and Methods: This was a case-control study. We included 80 neonates. The cases were divided into 2 groups; neonates with early-onset sepsis and control group with neonates non-sepsis. Apelin was quantified by enzyme-linked immunosorbent assay. Results: There was a significant elevation in the mean values of serum apelin in the early-onset sepsis group (1214.7 ± 273.06 pg/mmol) than in the non-septic neonates 116.27 ± 21.96 pg/mmol ( P < .0001). Apelin values were correlated to clinical sepsis and hematological scores as well as C-reactive protein. Serum apelin concentration was significantly higher among culture-positive cases than the culture-negative cases (mean ± SD was 1239.52 ± 268.47 and 929.42 ± 136.97 pg/mmol, respectively, P < .0001). Moreover, the apelin level was higher in non-survivor neonates than in the survivors in the early-onset sepsis group. No significant difference was found between preterm and full-term new-born infants with regard to the apelin values. The best cut-off estimate of apelin to diagnose early sepsis was >178.33 pg/mmol. Conclusion: Apelin may be useful in the diagnosis and prognostic prediction of neonates with early-onset sepsis.