Following acute brain injury (ABI), cellular hypoxia-ischaemia (CH-I) is central to the pathophysiological cascades that lead to death and neurological disability. Thus, a key tenet of neurocritical care is the avoidance of CH-I, and a key prerequisite to doing so is the availability of a bedside clinical monitor that can identify CH-I as it occurs. This thesis describes normal cerebral physiology, how this is deranged and clinically manipulated following ABI, and the use of near infrared spectroscopy (NIRS), a non- invasive optical technique, to monitor for CH-I in a variety of clinical contexts. I then present my work investigating the use of NIRS, with an emphasis on the measurement of the oxidation state of cytochrome c oxidase (CCO), in healthy volunteers who are subjected to a variety of challenges designed to manipulate cerebral oxygen delivery with both isovolaemic and hyper/hypovolaemic challenges. Finally, I describe experiments in a cohort of a patients who have suffered from ABI, manipulating cerebral oxygen delivery by means of normobaric hyperoxia. The results suggest that the measurement of CCO with NIRS in patients with ABI provides a useful adjunct to established monitors of cerebral haemodynamics and metabolism; an in-depth discussion of the observed changes in different haemodynamic and metabolic parameters, and their relevance to normal physiology and pathophysiology of ABI is carried out.