The arterovenous difference in carbon dioxide tension (DeltaPCO2) can be calculated after simultaneous sampling of arterial blood (PaCO2) and of mixed venous blood from the distal of a pulmonary artery catheter (PvCO2). Under physiological conditions, DeltaPCO2 ranges from 2 to 5 mmHg. The DeltaPCO2 depends on carbon dioxide and cardiac output by a complex fashion. In this article, we detail the influence of these factors on DeltaPCO2 in normoxic conditions and in hypoxic conditions. We bring evidence that DeltaPCO2 cannot serve as a marker of tissue hypoxia contrary to what was initially thought. However, DeltaPCO2 can be considered as a marker of the adequacy of venous blood flow (i.e. cardiac output) to remove the total CO2 produced by the peripheral tissues. In this regard, the knowledge of DeltaPCO2 should help the clinicians for the decision of giving therapy aimed at increasing cardiac output.