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Assess the prevalence of brain tissue hypoxia in patients with severe traumatic brain injuries (TBI), and to characterize the relationship between brain tissue hypoxia and functional outcome.Retrospective review of severe TBI patients.Intensive care unit of a level I trauma center.Twenty-seven patients with severe TBI requiring intracranial pressure (ICP) monitoring. Median age was 22 yrs, and a majority (63%) had traumatic subarachnoid hemorrhage.Hourly assessments of ICP, brain tissue oxygen, mean arterial pressure, fraction of inspired oxygen (Fio2), partial pressure of arterial carbon dioxide (Paco2), and hemoglobin concentration (hemoglobin) were recorded. Outcome was assessed 6–9 months postinjury.Mean (sd) ICP and BTpo2 were 13.7 (6.6) cm H2O and 30.8 (13.6) mm Hg. A total of 13.5% (379) of the BTpo2 values recorded were <20 mm Hg, only 86 of which were associated with ICP ≥20 cm H2O. This prevalence was comparable with episodes of ICP elevations above 20 cm H2O (14.1%, 397). Hypoxic episodes were more common when cerebral perfusion pressure was below 60 mm Hg (relative risk = 3.0, p < 0.0001). We did not find an association in hypoxic risk and hemoglobin in the range of 7–12 g/dL or Paco2 in the range of 25–40 mm Hg. Subjects with hourly episodes (epochs) of hypoxia >20% of the time had poorer scores on outcome measures compared with those with fewer hypoxic epochs.Hypoxic episodes are common after severe TBI, and most are independent of ICP elevations. Most episodes of hypoxia occur while cerebral perfusion pressure and mean arterial pressure are within the accepted target range. There is no clear association between Paco2 and hemoglobin with BTpo2. The young age and high prevalence of traumatic subarachnoid hemorrhage in this cohort may limit its generalizability. Increased frequency of hypoxic episodes is associated with poor functional outcome.