['To evaluate the ability of the central venous-to-arterial CO2 content and tension differences to arteriovenous oxygen content difference ratios (∆ContCO2/∆ContO2 and ∆PCO2/∆ContO2, respectively), blood lactate concentration, and central venous oxygen saturation (ScvO2) to detect the presence of global anaerobic metabolism through the increase in oxygen consumption (VO2) after an acute increase in oxygen supply (DO2) induced by volume expansion (VO2/DO2 dependence).', 'We prospectively studied 98 critically ill mechanically ventilated patients in whom a fluid challenge was decided due to acute circulatory failure related to septic shock. Before and after volume expansion (500\xa0mL of colloid solution), we measured cardiac index, VO2, DO2, ∆ContCO2/∆ContO2 and ∆PCO2/∆ContO2 ratios, lactate, and ScvO2. Fluid-responders were defined as a ≥15\xa0% increase in cardiac index. Areas under the receiver operating characteristic curves (AUC) were determined for these variables.', 'Fifty-one patients were fluid-responders (52\xa0%). DO2 increased significantly (31\xa0±\xa012\xa0%) in these patients. An increase in VO2\xa0≥\xa015\xa0% ("VO2-responders") concurrently occurred in 57\xa0% of the 51 fluid-responders (45\xa0±\xa016\xa0%). Compared with VO2-non-responders, VO2-responders were characterized by higher lactate levels and higher ∆ContCO2/∆ContO2 and ∆PCO2/∆ContO2 ratios. At baseline, lactate predicted a fluid-induced increase in VO2\xa0≥\xa015\xa0% with AUC of 0.745. Baseline ∆ContCO2/∆ContO2 and ∆PCO2/∆ContO2 ratios predicted an increase of VO2\xa0≥\xa015\xa0% with AUCs of 0.965 and 0.962, respectively. Baseline ScvO2 was not able to predict an increase of VO2\xa0≥\xa015\xa0% (AUC\xa0=\xa00.624).'] Are ratios of central venous-to-arterial carbon dioxide content or tension to arteriovenous oxygen content better markers of global anaerobic metabolism than lactate in septic shock patients?