BACKGROUND: Although global mortality rates in children under 5 years have decreased substantially in the last 30 years, there remain around 2.6 million stillbirths and 2.9 million neonatal deaths each year. The majority of these deaths occur in Africa and South Asia. To reduce perinatal deaths in East Africa, knowledge of the burden, but also the risk factors and causes of perinatal deaths are crucial. To the best of our knowledge, reviews have previously focused on the burden of perinatal deaths; here we aim to synthesize evidence on the burden, causes, and risk factors for perinatal mortality in East Africa. METHODS: We will conduct a systematic literature search in Medline, Web of Science, EMBASE, Global Health, SCOPUS, Cochrane Library, CINAHL, HINARI, African Index Medicus, African Journals Online (AJOL), and WHO African Regional Office (AFRO) Library. The study population includes all fetuses and newborns from ≥22 weeks of gestation (birth weight ≥500gm) to 7 days after birth, with reported causes or/and determinants as exposure, and perinatal mortality (stillbirths and/or early neonatal deaths) as an outcome. We will include studies from 2010 to 2022, and to facilitate the inclusion of up-to-date data, we will request recent data from ongoing surveillance in the region. To assess the quality of included studies, we will use the Joanna Briggs Institute quality assessment tool for observational and trial studies. We will analyze the data using STATA version 17 statistical software and assess heterogeneity and publication bias by Higgins' I 2 and funnel plot, respectively. CONCLUSIONS: This systematic review will search for published studies, and seek unpublished data, on the burden, causes, and risk factors of perinatal mortality in East Africa. Findings will be reported, and gaps in the evidence base identified, with recommendations, with the ultimate aim of reducing perinatal deaths. PROTOCOL REGISTRATION: PROSPERO-CRD42021291719.