One of the perceived difficulties with looking for evidence of occult brain injury in humans is the apparent need for CNS tissue specimens to prove that brain injury actually occurred. However, studies of stroke, trauma, and cardiopulmonary bypass-associated brain injury show that serum markers of brain injury correlate well with the extent of CNS damage. S-100β, neuron-specific enolase (NSE), and myelin basic protein (MBP) are three such markers that could be used to look for evidence of occult brain injury in critical illnessassociated CD.