Acute kidney injury (AKI) and fluid accumulation (FA) are common during extracorporeal membrane oxygenation (ECMO) support and are associated with increased morbidity and mortality. Despite their clinical importance, contemporary data describing the epidemiology and management of these conditions remain limited. Founded in 2021, the Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) seeks to improve outcomes for children requiring extracorporeal organ support. This report describes the design of the WE-ROCK ECMO study, an international, multicenter, retrospective cohort of patients supported with ECMO from 2018 to 2022. We include 1,264 children aged 0–25 years treated at 43 centers across 10 countries. Collected data include demographics, clinical characteristics before ECMO initiation, and detailed information from the first 14 days of ECMO support, including fluid intake and output, diuretic use, and continuous renal replacement therapy (CRRT) practices. Primary outcomes include major adverse kidney events at 90 days (mortality, dialysis dependence, and persistent kidney dysfunction) as well as functional status outcomes. The WE-ROCK ECMO study represents the largest international investigation of kidney and fluid-related variables in pediatric ECMO, providing critical insight into practice variation and the relationships among AKI, FA, CRRT, and clinical outcomes, and establishing a foundation for future interventional trials.