Maternal anxiety and stress-related mental health problems are a leading cause of preventable maternal perinatal deaths. They are associated with a 50% increase in severe maternal morbidity, as well as higher morbidity and poorer cognitive and mental health outcomes across children’s development. Yet, the causes of heightened vulnerability to anxiety and stress-related mental health problems in the perinatal period remain critically understudied and poorly understood. The proposed project aims to elucidate the causal mechanisms involved in the onset and maintenance of perinatal anxiety and stress-related symptoms. Specifically, the project will examine the putatively causal role of hormonal and immunological fluctuations in perinatal anxiety, and whether and how they interact with stress-exposure and cognitive vulnerabilities to heighten women’s susceptibility to mental health problems. Closing the translational loop, the project will examine causality by targeting the mechanisms involved in perinatal anxiety and stress-related symptoms with novel, scalable prevention tools. The project will realise these aims by combining innovative cross-species, longitudinal and experimental research in rats and women across the Global North and South. The project will be made possible by a collaboration between the team of international, interdisciplinary mental health researchers, women with lived experience, and a health professional advisory board.