Parameters such as central venous oxygen saturation (ScvO 2 ) are used increasingly to monitor adequate hemodynamic treatment. However, it still remains challenging to identify patients with assumed adequate circulatory status quantified by ScvO 2 who suffer from macro- and microcirculatory hypoperfusion. The authors hypothesized that central venous-arterial pCO 2 difference (dCO 2 ) could serve as an additional parameter to evaluate the adequacy of perfusion in cardiac surgery patients.Retrospective data analysis of a prospective interventional study.University medical center.Patients undergoing surgery with cardiopulmonary bypass.The dCO 2 was measured postoperatively. The patients with an ScvO 2 ≥70% were divided into 2 groups, the high-dCO 2 group (≥8 mmHg) and the low-dCO 2 group (<8 mmHg).Sixty patients were included in this analysis. Twenty-five patients had ScvO 2 ≥70%, 4 patients were assigned to the high-dCO 2 group. Patients of the high-dCO 2 group had significantly longer intensive care unit (ICU) stays (4 d; 1-29 v 1 d; 1-1; p = 0.02), significantly prolonged need for mechanical ventilation (41.5 h; 11-263.5; v 10 h; 7-11; p = 0.03), and higher cardiovascular complication rates in the ICU on postoperative days 3, 4, and 5 (p = 0.02). The mixed venous saturation (SvO 2 ) after 1 hour in the ICU was significantly lower, lactate levels were significantly higher, and the plasma disappearance rate of indocyanine green was significantly lower after 1 hour in the ICU (14.6%/min; 11.6-19.8%/min v 23.6%/min; 22.5-27.3%/min; p = 0.02) in the high-dCO 2 group. Cytokines increased significantly postoperatively in the high-dCO 2 group.The authors described dCO 2 as a routinely available tool to detect global and microcirculatory hypoperfusion in postoperative cardiac surgical patients. The authors showed that in patients with an ScvO 2 ≥70%, a high dCO 2 (≥8 mmHg) was associated with increased postoperative lactate levels and decreased splanchnic function. These findings were associated with a longer need for mechanical ventilation and longer ICU stay.