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Introduction Postoperative neuropsychological disorders including delirium, cognitive dysfunction and emotional distress are common after cardiac surgery and are linked to reduced quality of life, morbidity and mortality. Reliable preoperative risk factors remain difficult to identify. This study investigates stress-related parameters as predictors of postoperative neuropsychological disorders in patients undergoing cardiac surgery.Methods and analysis In this prospective study, 240 patients undergoing elective cardiac surgery (coronary artery bypass grafting: n=120, aortic valve replacement: n=120) with extracorporeal circulation at the Kerckhoff-Clinic Bad Nauheim (Germany) will be enrolled. Preoperative stress factors will be assessed using measures of stress-related personality traits, perceived stress, anxiety, depression, salivary cortisol and heart rate variability. Postoperative neuropsychological disorders will be evaluated through diagnosis of delirium in both the intensive care unit and on the standard ward. Additional neurocognitive dysfunctions and emotional distress will be assessed at hospital discharge and 3 months postoperatively, with corresponding preoperative baseline measurements.Discussion If stress measures prove to be predictive, they may enhance understanding of postoperative neurocognitive and emotional disorders and facilitate the development of risk stratification algorithms, enabling more effective preventive strategies for high-risk patients.Ethics and dissemination The study was approved by the Ethics Committee of Justus Liebig University Giessen (Ref.: 54/24) and is conducted in accordance with the Declaration of Helsinki. Written informed consent will be obtained from the patients. Results will be disseminated through peer-reviewed publications and scientific conferences.Trial registration number Prospectively registered with the German Clinical Trials Register (DRKS00035318).