Background: Delirium is common in critically ill patients and its presence is associated with increased mortality and increased likelihood of poor cognitive function among survivors. However, the cause of delirium is unknown. The purpose of this study was to demonstrate the feasibility of using near-infrared spectroscopy (NIRS) to assess brain tissue oxygenation in patients with septic shock, who are at high risk of developing delirium. Methods: This prospective observational study was conducted in a 33-bed general medical surgical intensive care unit (ICU). Patients with severe sepsis or septic shock were eligible for recruitment. The FORESIGHT NIRS monitor was used to assess brain tissue oxygenation in the frontal lobes for the first 72 hours of ICU admission. Physiological data was also recorded. We used the Confusion Assessment Method-ICU to screen for delirium.Results: From March 1st 2014-September 30th 2014, 10 patients with septic shock were recruited. The NIRS monitor captured 81% of the available data. No adverse events were recorded. Brain tissue oxygenation demonstrated significant intra- and inter-individual variability in the way it correlated with physiological parameters, such as mean arterial pressure, heart rate, and peripheral oxygen saturation. Mean brain tissue oxygen levels were significantly lower in patients who were delirious for the majority of their ICU stay. Conclusion: It is feasible to record brain tissue oxygenation with NIRS in patients with septic shock. This study provides the infrastructure necessary for a larger prospective observational study to further examine the relationship between brain tissue oxygenation, physiological parameters, and acute neurological dysfunction.