A central task in critical care medicine is the continuous maintenance of adequate tissue oxygenation. However, impairment of tissue perfusion and, thus, oxygenation is a common issue in critical care medicine, e.g., caused by anemia, cardiac failure or sepsis. If systemic oxygen delivery is reduced or maldistributed, certain organs may be impaired in oxygenation even before systemic markers of tissue dysoxia occur. Herein, the splanchnic region is particularly vulnerable in critical illness. Impaired splanchnic tissue perfusion and oxygenation play a crucial role in the development and maintenance of critical illnesses, e.g., the gastrointestinal tract may become the motor of sepsis and the multiple organ dysfunction syndrome. Thereby, the splanchnic region plays a role both as a target (e.g., through ischemia/reperfusion phenomena), but also as a source of the disease process (e.g., translocation of gastrointestinal endoluminal bacteria and toxins). Regarding the latter, continuous adequate microcirculatory oxygenation appears important to maintain the integrity of the gastrointestinal barrier function. The splanchnic region is not only affected by the disease process, but also by numerous therapeutic interventions, e.g., ventilation or drugs.