BackgroundThe current neonatal mortality rate in Uganda is high at 22 deaths per 1000 live births, while it had been stagnant at 27 deaths per 1000 live births in the past decade. This is still more than double the World Health Organization target of < 12 deaths per 1,000 live births. Three-quarters of new born deaths occur within the first week of life, which is a very vulnerable period and the causes reflect the quality of obstetric and neonatal care. At Mbarara Regional Referral Hospital (MRRH), the modifiable contributors and predictors of mortality remain undocumented, yet neonates make the bulk of admissions and contribute significantly to the overall infant mortality rate. We therefore examined the clinical profiles, incidence and predictors of early neonatal mortality of neonates admitted at MRRH in south-western Uganda.MethodsWe conducted a prospective cohort study at the Neonatal Unit of MRRH between August – November, 2022 among neonates. We consecutively included all live neonates aged < 7 days admitted to neonatal unit and excluded those whose outcomes could not be ascertained at day 7 of life. We obtained baseline data including; maternal social-demographic and obstetric information, and performed neonatal physical examinations for clinical profiles. We followed up neonates at 24 and 72 h of life, and at 7 days of life for mortality. We summarized the clinical profiles and incidence of mortality as frequencies and percentages and performed modified Poisson regression analysis to identify the predictors of early neonatal mortality.ResultsWe enrolled 384 neonates. The majority of neonates were in-born (68.5%, n = 263) and were admitted within 24 h after birth (54.7%, n = 210). The most common clinical profiles at admission were prematurity (46%, n = 178), low birth weight (LBW) (44%, n = 170), sepsis (36%, n = 139), hypothermia (35%, n = 133), and birth asphyxia (32%, n = 124). The incidence of early neonatal mortality was at 12.0%, 46 out of the 384 neonates died. The predictors of early neonatal mortality were hypothermia, [adjusted Risk Ratio: 4.10; 95% C.I (1.15–14.56)], birth asphyxia, [adjusted Risk Ratio: 3.6; 95% C.I (1.23–10.73)] and delayed initiation of breastfeeding, [adjusted Risk Ratio: 7.20; 95% C.I (1.01–51.30)].ConclusionPrematurity, LBW, sepsis, birth asphyxia and hypothermia are the commonest admission diagnoses. The incidence of early neonatal mortality was high, 12.0%. We recommend targeted interventions by the clinical care team at MRRH to enable timely identification of neonates with or at risk of hypothermia to reduce incidence of adverse outcomes. Intrapartum care should be improved in order to mitigate the risk of birth asphyxia. Breastfeeding within the first hour of birth should be strengthened were possible, as this is associated with vast benefits for the baby and may reduce the incidence of complications like hypothermia.