Abstract Introduction The study of crisis events provides important lessons to prepare for upcoming events. The Great Recession’s impact on perinatal health in Europe can provide relevant insights into the healthcare and social protection systems’ response to protecting the health of the most vulnerable groups. Objectives To assess time trends and international disparities in perinatal mortality rates (PMR) and infant mortality rates (IMR), following the Great Recession, and their association with socioeconomic indicators in Portugal, Greece, Italy and Spain. Methods Associations were assessed through generalised linear models for all four countries. A Poisson joinpoint regression model was applied to explore PMR and IMR trend changes between 2000 and 2018. Country disparities were analysed using mixed-effects multilevel models. Results IMR and PMR have decreased overall in the four selected countries between 2000 and 2018. Still, whereas in Spain, Italy and Portugal the decreasing pace was attenuated after 2009, in Greece a positive trend was found after the 2008 crisis. IMR and PMR were significantly associated with socioeconomic indicators in all four countries. National disparities in the evolution of IMR and PMR were significantly associated with most socioeconomic indicators between 2000 and 2018. Conclusions Our results confirm the impact of the Great Recession on PMR and IMR trends in all four countries, taking recurring associations between macroeconomic cycles, variations in mortality trends, macroeconomic volatility and stagnation of IMR and PMR into account. The association with socioeconomic indicators stresses the need to strengthen social protection and healthcare systems to better protect the population’s health from the earliest days. Key messages • Mortality patterns refer to the internal variability of the crisis’ effect and to persistent spatial regional inequalities appealing to the need for attention in policymaking. • The relevance of considering the political economy of global health finance and macroeconomic volatility as a major influence on the association of mortality rates with socioeconomic indicators.