High-pressure excursions (HPE) during cardiopulmonary bypass (CPB) are rare but potentially life-threatening events linked to coagulation activation, inflammation. Known risk factors include male sex, large body surface area (BSA), elevated hematocrit (Htc), prior stroke and urgent surgery. Recommended management follows a stepwise approach involving haemodilution, heparin and antithrombin (AT), albumin or epoprostenol depending on Htc and pressure thresholds. We report a 69-year-old man undergoing urgent complex cardiac surgery who developed rising pre-oxygenator pressures 10 min after CPB initiation. Despite initial haemodilution and AT, pressures improved only partially. Administration of 100 mL of 20% albumin led to rapid normalization of pre-oxygenator and delta pressures, allowing safe continuation of CPB. The postoperative course was uneventful. Subsequent review of the oxygenator transmembrane resistance (R) showed a progressive decline following the administration of AT and albumin. This case suggests that AT, administered alongside albumin, may reduce blood viscosity and improve oxygenator performance. Further research is needed to clarify mechanisms and standardize management of HPE during CPB.