The primary end point when treating acute shock is to restore blood circulation, mainly by reaching macrocirculatory parameters. However, even if global haemodynamic goals can be achieved, microcirculatory perfusion may remain impaired, leading to cellular hypoxia and organ damage. Interestingly, few methods are currently available to measure the adequacy of organ blood flow and tissue oxygenation. The rise in tissue partial pressure of carbon dioxide (CO2) has been observed when tissue perfusion is decreased. In this regard, tissue partial pressure of CO2 has been proposed as an early and reliable marker of tissue hypoxia even if the mechanisms of tissue partial pressure in CO2 rise during hypoperfusion remain unclear. Several technologies allow the estimation of CO2 content from different body sites: vascular, tissular (in hollow organs, mucosal or cutaneous), and airway. These tools remain poorly evaluated, and some are used but are not widely used in clinical practice. The present review clarifies the physiology of increasing tissue CO2 during hypoperfusion and underlines the specificities of the different technologies that allow bedside estimation of tissue CO2 content.