Ketone bodies (KBs) are energy-efficient substrates utilized by the heart depending on its metabolic demand and substrate availability. Levels of circulating KBs have been shown to be elevated in acute and chronic cardiovascular disease and are associated with severity of disease in patients with heart failure and functional outcome after myocardial infarction. To investigate whether this pattern similarly applies to patients undergoing cardiac surgery involving cardiopulmonary bypass (CPB), we analysed prospectively collected pre- and postoperative blood samples from 192 cardiac surgery patients and compared levels and perioperative changes in total KBs with Troponin T as a marker of myocardial cell injury. We explored the association of patient characteristics and comorbidities for each of the two biomarkers separately and comparatively. Median levels of KBs decreased significantly over the perioperative period and inversely correlated with changes observed for Troponin T. Associations of patient characteristics with ketone body perioperative course showed notable differences compared to Troponin T, possibly highlighting factors acting as a “driver” for the change in the respective biomarker. We found an inverse correlation between perioperative change in ketone body levels and changes in troponin, indicating a marked decrease in ketone body concentrations in patients exhibiting greater myocardial cell injury. Further investigations aimed at better understanding the role of KBs on perioperative changes are warranted.