The aim of our study was to perform and in-depth analysis of several episodes of regional brain hypoxia detected by monitoring brain partial pressure of oxygen (PtiO2) in which simultaneous measurements of cerebral oxygen extraction fraction (O2EF) suggested a normally perfused or even a hyperemic brain. To gain deeper insight into these episodes, we used the model of tissue hypoxia described by Siggaard-Andersen. In 244 simultaneous measurements, 31 episodes (12.7%) of brain hypoxia (PtiO2 < or = 15 mmHg) were detected simultaneously with an O2EF within the normal range or below the lowest normal percentile. Using Siggaard-Andersen methodology, we classified 6 episodes (19%) as high-affinity hypoxia and 25 (81%) as shunt hypoxia or dysperfusion hypoxia. Siggaard-Andersen's comprehensive classification of tissue hypoxia can be used as an integrative model to build coherent algorithms for diagnosing and managing neurocritical patients that are at risk of brain hypoxia due to either intracranial or extracranial conditions.