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In this study cerebral oxygenation was measured using the NIRO 300 and the INVOS 5100 spectrophotometers in 10 healthy adult volunteers, exposed to varying degrees of hyperoxia and hypoxia. The results showed similar baseline values for tissue oxygenation index and regional cerebral oxygen saturation with mean (SD) values being 64.9% (5.1) and 62.3% (6.0), respectively. The overall bias was –2.1%, with the INVOS 5100 under-reading cerebral oxygenation compared to the NIRO 300, with limits of agreement of ±14.7%. Both monitors demonstrated similar changes in response to hyperoxia and hypocapnia (coefficient of variance for FIO2 0.45 = 10.0%, FIO2 1.0 = 10.1%, hypocapnia = 14.5%). The reasons for the bias and variability may relate to differences in the methodological approaches of the two monitors. The correlation between the monitors in response to changes in cerebral oxygenation implies that they may be useful as trend monitors in clinical practice.