The respiratory exchange ratio (RER), defined as the ratio of carbon dioxide (CO₂) production to oxygen (O₂) consumption, may be a non-invasive and continuously measurable alternative to lactate for identifying patients at risk of postoperative complications that has been examined in non-cardiac surgery. We investigated whether intraoperative RER predicts blood lactate levels and postoperative complications in cardiac surgery. This retrospective cohort study included adult patients undergoing cardiac surgery with cardiopulmonary bypass at Beth Israel Deaconess Medical Center in Boston, USA, between 2008 and 2020. Intraoperative minute-by-minute data of inspired and expired fractions of CO₂ and O₂ were analyzed. Univariable and a priori-defined multivariable logistic regression models were used to evaluate the association between the median RER during surgery, intraoperative lactate and 7-day major postoperative complications (European Perioperative Clinical Outcome Definitions). 324,646 RER calculations of 4,058 patients were included. 1,745 (43.0%) patients experienced 7-day postoperative complications. The median (IQR) RER was 0.64 (0.48–0.92) before and 0.65 (0.48–0.97) after bypass. The RER within 10 min prior to lactate testing was associated with lactate levels > 2 mmol/l (adjusted odds ratio [OR_adj] 1.11, 95% confidence interval [CI] 1.01–1.23, p = 0.031). Neither RER before nor after bypass was associated with 7-day postoperative complications (before bypass: OR_adj 1.02, 95%CI 0.95–1.10, p = 0.55; after bypass: OR_adj 1.03, 95%CI 0.95–1.13, p = 0.46). While RER showed a modest relationship with hyperlactatemia, its utility as a predictor of postoperative complications appears limited in real-world data. Further research is needed to clarify its role and potential for clinical applicability.