OBJECTIVES: To investigate copeptin levels during the full perioperative course in open, adult cardiac surgery with cardiopulmonary bypass (CPB). DESIGN: Prospective cohort study. SETTING: A single-center study conducted in a tertiary care hospital. PARTICIPANTS: We included 61 patients undergoing various cardiac surgical procedures. In the final analysis, 57 patients were evaluated. Patients were divided into 2 subgroups based on preoperative copeptin levels, either above or below the reference level of 10 pmol/L. INTERVENTIONS: No intervention. MEASUREMENTS AND MAIN RESULTS: Copeptin levels were measured at multiple time points preoperatively, perioperatively, and postoperatively. Copeptin levels significantly increased from a preoperative median of 6.6 pmol/L (interquartile range [IQR], 3.9-11.0) to 27 pmol/L (IQR, 15.0-66.0 pmol/L) after sternotomy (p ≤ 0.002). Peak levels occurred 60 minutes after CPB initiation, reaching 286 pmol/L (IQR, 163-446 pmol/L). After this, the copeptin levels did not drop significantly until CPB termination at 179.5 pmol/L (IQR, 136.0-346.0 pmol/L) (p ≤ 0.002). Subsequent decreases were observed upon arrival in the intensive care unit and throughout the postoperative period. However, at 4 days postoperatively, copeptin levels remained significantly higher (11.5 pmol/L
IQR,7.2-19.0 pmol/L
p ≤ 0.002), than preoperative levels. CONCLUSIONS: This study describes copeptin levels during the perioperative course in adult cardiac surgery. The elevated levels during CPB suggest a strong activation of the arginine vasopressin system, with peak levels exceeding those seen in septic shock. This knowledge will enable further targeted clinical studies on copeptin as a prognostic marker in the field of cardiac surgery.