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Main problems of critical illness and sepsis are an altered oxygen distribution and microvascular dysfunction linked to tissue oedema. This review seeks to analyse the role of the endothelial glycocalyx in this context.The presence of vascular leakage is typically associated with interstitial oedema, arterial hypotension, hypovolaemia and often a bad outcome in patients with systemic inflammation. Early goal-directed therapy provides significant benefits in severe sepsis and septic shock, but is mostly aimed at improving macrohaemodynamics. Recent data suggest that microcirculation also contributes significantly to the pathophysiology of critical illness. In fact, the endothelial glycocalyx plays a major role in vascular barrier competence. According to experimental evidence, it can easily be degraded in the presence of inflammation, but, theoretically also protected by several measures. Clinical studies revealed a positive correlation of the severity of sepsis and ischaemia with mortality, but also with a deterioration of the endothelial glycocalyx. Future investigation should focus on the preservation of this structure and assess microcirculatory variables to judge the success of cardiocirculatory therapy.Deterioration of the endothelial glycocalyx initiates a breakdown of the vascular barrier in systemic inflammatory response syndrome and sepsis. Preserving this structure in critical illness might be a future therapeutical goal to improve microcirculatory oxygen distribution.