Levels of jugular blood oxygen saturation (SjvO2) and lactate have been proposed as indicators of cerebral ischemia and prognosis. However, sensitivity and specificity of these markers remain unknown. We retrospectively analyzed records of a series of 43 comatose patients at risk for cerebral ischemia, mainly after head injuries or subarachnoidal hemorrhage. Their SjvO2, jugulo-arterial lactate difference (VADLactate), and lactate-oxygen index (LOI) were determined every 8 hours. An increase in VADLactate and LOI was found, indicative of ischemia on CT scan, with threshold values of 0.30 mmol/L and 0.15, respectively. Sensitivity and specificity were 100% and 64%, respectively, for the VADLactate threshold, and 90% and 55%, respectively, for the LOI threshold. Regarding prediction of a poor outcome, only an increase in VADLactate had a predictive value with a sensitivity of 100% and specificity of 67%. No threshold value with sufficient sensitivity and specificity was found for SjvO2, as indicator of either ischemia or outcome. During progression to brain death, VADLactate and LOI reached abnormal levels earlier than cerebral perfusion pressure or SjvO2. They reacted markedly to focal ischemia due to vasospasm. Hyperlactacidemia rendered VADLactate and LOI uninterpretable by causing a brain lactate influx. Present data, if confirmed by a prospective study, would justify inclusion of intermittent VADLactate and LOI determinations in the multimodal cerebral monitoring.