Background: Disease outbreaks significantly affect maternal and neonatal health. Variability in reporting health outcomes hinder evidence generation. We aimed to develop a core outcome set (COS) for maternal and neonatal health research and surveillance during emerging and ongoing epidemic threats and to agree on outcomes’ definitions. Methods: We conducted a systematic review of observational and experimental studies related to epidemics to identify outcomes, and a four-stage modified-Delphi consensus. 150 international stakeholders participated in online surveys, and 24 representatives in consensus meetings. The panels were diverse, with balanced representation of professional background, gender, and geography, including civil society representatives. Outcome were included if ≥ 80% of participants scored them as critically important and ≤10% rated them as not important. Findings: The final COS includes seven main maternal outcomes—pregnancy outcome, maternal death, suspected symptomatic infection, confirmed infection, severe disease, preterm delivery, mode of birth; seven complementary maternal outcomes—antepartum haemorrhage, postpartum haemorrhage, hypertensive disorders of pregnancy, maternal sepsis, admission to intensive care unit/special units, respiratory support, depression and anxiety; 11 main neonatal outcomes—neonatal death, neonatal suspected symptomatic infection, confirmed infection, severe disease, vertical transmission, low birth weight, prematurity, congenital disorder, respiratory support, skin-to-skin contact, breastfeeding; and, four complementary neonatal outcomes—admission to neonatal intensive care unit/special units, respiratory failure, birth asphyxia, sepsis. Interpretation: This COS could contribute to standardize maternal and neonatal outcomes selection and reporting in observational and experimental studies, facilitating efficient data comparison and timely evidence-based decision-making in the context of ongoing and emerging epidemic threats. Funding: Bill & Melinda Gates Foundation (grant INV-041181) and the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), a cosponsored programme executed by the World Health Organization (HQHRP2422779).