BackgroundNeonatal sepsis is a leading cause of neonatal death across the globe, which accounted 15% and 30% of neonatal mortality in low and middle income and developing countries including Ethiopia, respectively. Despite various efforts have been made by Ethiopian government to prevent neonatal mortality and morbidity, sepsis related to neonatal mortality is still high. So the objective of this study was to assess the magnitude and affecting factors of neonatal sepsis among neonate admitted to neonate intensive care units in Hawassa University Comprehensive Specialized Hospital, Southern Ethiopia.Methods and materialsFacility based cross-sectional study was conducted from January to February, 2022 at Hawassa university comprehensive specialized hospital, Southern Ethiopia. The total of 216 neonate-mother pairs who were admitted to intensive care unit was included in the study and a systematic random sampling technique was used to select study participant. Structured questionnaire was used to collect data. The data was entered in to EPI Data 3.1 version transported to SPSS version 25 for data analysis. Multi regression analysis was done for predictor variables associated at p-value < 0.05 with the dependent variable.ResultA total of 74 (34.3%) neonates were admitted with neonatal sepsis. A surgical procedure is done before sepsis (AOR = 2.9, 95% of CI(1.5 to5.6), last pregnancy wanted (AOR = 2.8, 95% of CI(1.0 to 7.3), more frequent per-vaginal examination (AOR = 2.6, 95% of CI (1.3 to 5.3), educational level unable to read and write(AOR = 5.4, 95% of CI(1.0 to 27.7), low birth weight (AOR = 5.4, 95% of CI(3.0 to 9.8), and getting care from unskilled health workers(AOR = 2.7, 95% of CI(1.5 to 4.9) were significantly associated with neonatal sepsis at multivariable with less than 0.05 p values.ConclusionThis study indicated that the prevalence of neonatal sepsis was still high. Thus, immediate action should be taken before it leads to neonatal mortality and further complications. The study used only physician diagnosis to confirm neonatal sepsis, which may affect its prevalence and needs further investigation.