BACKGROUND: The decision-making process for red blood cell transfusion (RBCT) in critically ill patients in the intensive care unit (ICU) remains primarily guided by hemoglobin-based thresholds. However, as a component of personalized medicine, innovative and individualized criteria should be developed to optimize RBCT decisions. This study aims to assess the impact of RBCTs on oxygenation parameters and patient outcomes, with a specific focus on the oxygen extraction ratio (O STUDY DESIGN AND METHODS: This prospective observational study included 77 critically ill patients receiving RBCTs according to ICU transfusion protocols. The primary hypothesis is that patients with an O RESULTS: The O DISCUSSION: Our study reveals promising insights into the impact of RBCTs on O TRIAL REGISTRATION NUMBER: NCT05798130 (https://clinicaltrials.gov/study/NCT05798130).