Background Venoarterial carbon dioxide pressure (pv-aCO2) and content (Cv-aCO2) differences, including the ratio to arteriovenous oxygen content difference (Ca-vO2), and free energy changes (−∆∆Ga-v) may reflect tissue hypoperfusion. The associations with changes in cardiac output (CO) or oxygen consumption (VO2) following fluid bolus administration were investigated. Methods Single-centre, observational study of 89 adult post-operative cardiac surgical patients admitted to ICU. The pv-aCO2, Cv-aCO2 and their ratios to Ca-vO2 as well as the −∆∆Ga-v were determined before and after a 250-500 mL fluid bolus using arterial, central venous and mixed venous blood gas analyses. Responses associated with changes ≥ or <15% in CO or oxygen consumption (VO2) were compared. Results In 234 boluses, the mixed venous to arterial pv-aCO2 and its ratio to Ca-vO2 were independently associated with an increase in CO; odds ratio 1.3 (95% CI 1.1-1.5) and 1.7 (95% CI 1.5-1.9) respectively, P <.001) and VO2; odds ratio 2.1 (95% CI 1.3-3.1), P <.001 for Ca-vO2. No measures of pv-aCO2, Cv-aCO2 or related ratios to the Ca-vO2 were associated with an increase in CO ≥15% following a single volume bolus. The mixed venous and central venous Cv-aCO2 to Ca-vO2 ratios were different for the first bolus episode only; mean differences 0.81 (95% CI 0.13-1.5), P =.02 and 0.44 (95% CI 0.06-0.82), P =.02, respectively, for increased VO2 ≥ 15%. The −∆∆Ga-v did not change. Conclusion The venoarterial carbon dioxide gradients and related calculations to assess the adequacy of tissue perfusion before a fluid bolus were not associated with subsequent increases in CO of oxygen consumption.