BackgroundGlobally, neonatal sepsis is the leading cause of neonatal mortality and morbidity, particularly in developing countries. Despite studies that revealed the prevalence of neonatal sepsis in developing countries, the outcome of the diseases, barriers for poor outcomes were inconclusive. The aim of this study was to assess the treatment outcome of neonatal sepsis and its associated factors among neonates admitted to neonatal intensive care unit in public hospitals, Addis Ababa, Ethiopia, 2021.MethodsA cross-sectional study was carried out from February 15 to May 10, 2021 on 308 neonates admitted to neonatal intensive care units of Addis Ababa city public hospitals. Hospitals and study participants were selected by lottery and systematic random sampling techniques, respectively. Data were collected through face-to-face interviews with a structured, pretested questionnaire and by reviewing both the maternal and newborn profile cards. Epi-data version 4.6 was used to enter the collected data, which was then exported to SPSS version 26 for analysis. The 95% CI odds ratio is used to determine the direction and strength of the association between the dependent and independent variables.ResultsAmong the total study 308 neonates, 75(24.4%) were died. Regarding the poor treatment outcome of neonatal sepsis, neonates whose mothers <37 weeks of gestational age (AOR = 4.87, 95% CI: 1.23–19.22), Grunting (AOR 6.94: 1.48–32.54), Meconium amniotic stained (AOR = 3.03, 95% CI: 1.02–9.01), Duration of rupture of membrane >18hours (AOR = 3.66, 95% CI: (1.20–11.15), Hypertensive PIH/ Eclampsia (AOR = 3.54, 95% CI: 1.24–10.09), Meropenum (AOR = 4.16, 95% CI: 1.22–14.21) and CRP positive result (AOR = 5.87, 95% CI: 1.53–22.56) were significantly associated with poor treatment outcome of neonatal sepsis.Conclusion and recommendationThe treatment outcomes of neonates were 75.6% recovered and 24.4% died. In this setting, empirical treatment was the cornerstone for managing neonatal sepsis. Professionals who are working in labor and delivery ward screened for mothers preeclampsia and duration of rupture of membrane >18hrs /PROM/ treated with antihypertensive drug and antibiotics for the prevention of neonatal sepsis.