Left ventricular assist device (LVAD) explant heart transplantation represents a metabolically vulnerable population with an increased risk for renal failure and mortality. Oxygen extraction ratio (O₂ER), which integrates oxygen delivery and tissue oxygen demand, may provide a physiologic marker of cumulative metabolic stress during cardiopulmonary bypass (CPB). Adult LVAD-explant heart transplant recipients at a single center from October 2021 to June 2025 were analyzed using continuous perfusion data captured during CPB. Oxygen extraction ratio was calculated continuously, and cumulative oxygen extraction burden was quantified as the area above an O₂ER threshold of 0.20. Patients were stratified by median O₂ER burden. Among 110 patients, a higher intraoperative O₂ER burden was associated with increased postoperative renal replacement therapy (odds ratio [OR], 4.16; 95% confidence interval [CI], 1.35–12.83) and increased 2-year mortality (hazard ratio [HR], 7.61; 95% CI, 1.49–38.73) after inverse probability weighting adjustment. A higher O₂ER burden was also associated with a lower immediate postoperative cardiac index and increased vasoactive inotrope requirements. Donor hypertension, recipient diabetes, static storage modality, and a lower intraoperative oxygen delivery index were associated with an increased O₂ER burden. These findings suggest that cumulative oxygen extraction during CPB reflects intraoperative metabolic stress and may represent a physiologically integrated perfusion target in LVAD-explant heart transplantation.