Abstract: An anesthetized sheep model of traumatic brain injury (TBI) has been developed to assess early changes in intracranial pressure (ICP) following closed head injury. Immediately after TBI, a transient (<10 min) hypertensive response occurred, followed by significant and prolonged systemic hypotension. ICP demonstrated a biphasic response, being seven times baseline values of 8 ± 2 mm Hg 10 min after injury, decreasing to 25 ± 2 mm Hg by 30 min, and then increasing to values exceeding 30 mm Hg by 4 h postinjury. ICP was always significantly higher than baseline values, which combined with hypotension, reduced cerebral perfusion pressure to less than 60% of normal. This early and sustained increase in ICP after craniocerebral trauma acutely alters cerebral perfusion pressure and brain oxygenation and provides a potential pathophysiological explanation for immediate clinical manifestations in humans following significant TBI.