Sepsis is among the most common reason for admission to intensive care units throughout the world. Sepsis is characterized by a generalized microcirculatory injury, which results in tissue dysoxia. Tissue dysoxia is believed to be the causation of multiorgan dysfunction syndrome (MODS) which commonly complicates the course of sepsis. The expedient detection and correction of tissue dysoxia may limit the development of MODS. The standard oxygenation and hemodynamic variables (blood pressure, arterial oxygenation, cardiac output) which are monitored in critically ill patients are “upstream” markers and provide little information as to the adequacy of tissue oxygenation. Global “downstream” markers of tissue dysoxia such as mixed venous oxygen saturation and blood lactate are insensitive indicators of the extent of the microcirculatory injury in patients with sepsis. Sublingual/buccal mucosal PCO2 is a regional marker of microvascular perfusion and tissue dysoxia that holds great promise for the risk stratifi cation and endpoint of goal-directed resuscitation in patients with sepsis.