A defining characteristic of sepsis is progressive blood flow dysfunction in the microvasculature in organs remote to the original site of injury. Previous work has established that microvascular oxygen transport is compromised in sepsis due to a loss of perfused capillaries. In a companion study to this project, which investigated the role of leukocyte traffic in sepsis, it was observed that increased transit times of leukocytes passing through the capillary bed not only resulted in the occlusion of some capillaries but also served to cause some vessels to experience prolonged periods of low flow. The objective of the present study was to examine how the progressive loss of functional capillary density (FCD) impacts oxygen transport and consumption in skeletal muscle during sepsis. Hemodynamic and oxygen saturation data from video recordings are incorporated into an experiment-based mathematical model of oxygen transport in a 3D volume. This modeling helps to further our understanding of the impact capillary loss has on tissue oxygenation and consumption. Sepsis was induced in rats by cecal ligation and perforation (CLP). Rats received crystalloid fluid resuscitation to maintain the blood pressure and hematocrit at baseline levels. Microvascular flow was observed in the extensor digitorum muscle using a dual wavelength intravital video microscopy set-up. The same field of view was recorded at 30-min intervals between 2 and 5 hours post CLP to follow the progression of capillary dysfunction. Individual capillaries were analyzed for oxygen saturations and hemodynamics. As sepsis progressed we observed that the capillaries' hemodynamic profiles transiently change between normal, stopped and fast flow states. Although it has previously been assumed that once a capillary becomes occluded flow is not easily re-established, we observed that capillaries could suddenly become reperfused after being occluded for up to 1 hour or more. The occlusion of capillaries was found to decrease oxygen saturations in nearby vessels by as much as 20%. Subsequent recruitment of previously unperfused capillaries was shown to increase saturations in adjacent vessels by as much as 50%. Changes in perfusion of adjacent vessels had a greater impact on oxygen saturations than changes in hematocrit or velocity in the vessel itself. At 2, 3 and 4 hours post CLP the percentage of stopped flow vessels was 17%, 28% and 48% in CLP compared with 13%, 13% and 20% in sham. The extent of FCD loss is progressive over the course of the injury. However, it is important to note that while the percentage of occluded capillaries increases, the individual vessels constituting this percentage were variable. Our study suggests that in this early stage where the FCD is in transition, affected tissue experiences dynamic changes in tissue oxygenation. This highlights the importance of understanding the mechanisms responsible for this dynamic change in FCD.