SummaryBackgroundChild mortality is high in Ethiopia, but reliable data on the causes of death are scarce. We aimed to gather data for the contributory causes of stillbirth and child deaths in eastern Ethiopia.MethodsIn this population-based post-mortem study, we established a death-notification system in health facilities and in the community in Kersa (rural), Haramaya (rural) and Harar (urban) in eastern Ethiopia, at a new site of the Child Health and Mortality Prevention Surveillance (CHAMPS) network. We collected ante-mortem data, did verbal autopsies, and collected post-mortem samples via minimally invasive tissue sampling from stillbirths (weighing at least 1000 g or with an estimated gestational age of at least 28 weeks) and children who died younger than 5 years. Children—or their mothers, in the case of stillbirths and deaths in children younger than 6 months—had to have lived in the catchment area for the past 6 months to be included. Molecular, microbiological, and histopathological analyses were done in collected samples. Cause of death was established by an expert panel on the basis of these data and classified as underlying, comorbid, or immediate separately for stillbirths, neonatal deaths (deaths aged 0–27 days), and child deaths (aged 28 days to <5 years).FindingsBetween Feb 4, 2019, and Feb 3, 2021, 312 deaths were eligible for inclusion, and the families gave consent in 195 (63%) cases. Cause of death was established in 193 (99%) cases. Among 114 stillbirths, the underlying cause of death was perinatal asphyxia or hypoxia in 60 (53%) and birth defects in 24 (21%). Among 59 neonatal deaths, the most common underlying cause was perinatal asphyxia or hypoxia (17 [29%]) and the most common immediate cause of death was neonatal sepsis, which occurred in 27 (60%). Among 20 deaths in children aged 28 days to 59 months, malnutrition was the leading underlying cause (15 [75%]) and infections were common immediate and comorbid causes. Pathogens were identified in 19 (95%) child deaths, most commonlyKlebsiella pneumoniaeandStreptococcus pneumoniae.InterpretationPerinatal asphyxia or hypoxia, infections, and birth defects accounted for most stillbirths and child deaths. Most deaths could have been prevented with feasible interventions, such as improved maternity services, folate supplementation, and improved vaccine uptake.FundingBill & Melinda Gates Foundation.