Background: A rare but important complication related to otherwise uneventful brain and spine surgery is becoming more recognized and more frequently reported in the medical literature. This has been variably labeled as pseudohypoxic brain swelling or postoperative hypotension-associated venous congestion. This poorly understood condition occurs in the setting of surgical intervention and is thought to be related to cerebrospinal fluid leak or evacuation, decreased intracranial pressure, and subsequent development of deep venous congestion affecting the basal ganglia, thalami, and cerebellum. Clinically, patients may have global neurologic deficit and outcomes range from full recovery to vegetative state or death. The imaging correlate includes atypical edema, infarction, or hemorrhage and can overlap the appearance of diffuse hypoxic injury, for which this condition can be mistaken both clinically and radiologically. Although this deep brain tissue edema can be associated with other signs of cerebrospinal fluid hypotension such as dural thickening, brain sagging, and cerebellar herniation, it can be isolated, making the diagnosis challenging. Case Description: We present 2 cases of unexpected clinical deterioration occurring in patients with otherwise uncomplicated neurosurgery, 1 with craniotomy and the other with lumbar spine intervention. Both patients exhibit similar appearing edema in the deep gray structures on postoperative magnetic resonance imaging scans. In addition to reviewing the prior literature and imaging findings, we evaluate the imaging findings to determine if there are unique features or signatures that might allow differentiation of PHBS from hypoxic-ischemic encephalopathy. Conclusions: The lentiform rim sign can be helpful for differentiation of pseudohypoxic brain swelling versus hypoxic-ischemic encephalopathy.