Background: A common neurological complication of critical illness is delirium, defined as an acute change in level of consciousness, with impaired attention and disorganized thinking. Patients with delirium have increased risk of long-term cognitive dysfunction and mortality. The cause is unknown, which limits our ability to design therapeutic interventions. In patients undergoing surgery, low regional cerebral oxygenation (rSO2), as measured by near-infrared spectroscopy (NIRS), is associated with postoperative neurological dysfunction (eg delirium and long-term cognitive impairment). However, the relationship between NIRS-derived rSO2 and neurological outcomes in critically ill patients is unclear. The objective of this study was to assess the utilization of NIRS-derived rSO2 in critically ill patients outside the operating theater. We aimed to examine the relationship between rSO2 and neurological outcomes as well as to report rSO2 values in this population. Methods: The following databases were searched from inception to August 14, 2017: Ovid MedLine, Embase, Cochrane Library, and Web of Science. Results: Of 1410 articles identified by the search strategy, 8 were ultimately selected for final review. Most (7 of 8) were published since 2014. These studies included a total of 213 patients primarily with shock or respiratory failure. A variety of devices were used to measure rSO2, including INVOS and FORESIGHT. The duration of recording varied from 5 minutes to 72 hours. Four of the 8 studies reported on neurological outcomes. In all 4 studies, rSO2 was lower in critically ill patients who were delirious compared to controls, but this was only statistically significant in 2 of the studies. The heterogeneity in devices and duration of recording precluded meta-analysis. Conclusions: There is limited literature describing rSO2 in critically ill patients outside the operating room. Although there may be a slight signal of an association between low rSO2 and delirium, more study is needed to explore this relationship.