This long-term septic model exhibited an early decline in tissue oxygenation, the degree of which related to predicted mortality. Clinical and biochemical deterioration, however, progressed despite cardiovascular recovery. Early circulatory dysfunction may thus be an important trigger for downstream processes that result in multi-organ failure. Furthermore, the utility of tissue PO2 monitoring to highlight the local oxygen supply-demand balance, and dynamic O2 challenge testing to assess microcirculatory function merit further investigation.