Cerebral fractional oxygen extraction (FOE) represents the balance between cerebral oxygen delivery and consumption. This study aimed to determine cerebral FOE in preterm infants during hypotension, during moderate anemia, and with changes in the PaCO2. Three groups of neonates were studied: stable control neonates (n = 43), anemic neonates (n = 46), and hypotensive neonates (n = 19). Cerebral FOE was calculated from the arterial oxygen saturation measured by pulse oximetry, and cerebral venous oxygen saturation was measured using near infrared spectroscopy with partial jugular venous occlusion. Mean +/- SD cerebral FOE was similar in control (0.292+/-0.06), anemic (0.310+/-0.08; P = 0.26), and hypotensive (0.278+/-0.06; P = 0.41) neonates. After anemic neonates were transfused, mean +/- SD cerebral FOE decreased to 0.274+/-0.05 (P = 0.02). There was a weak negative correlation with the hemoglobin concentration (n = 89, r = -0.24, P = 0.04) but not with the hemoglobin F fraction (n = 56, r = 0.24, P = 0.09). In the hypotensive neonates, there was no relationship between cerebral FOE and blood pressure (n = 19, r = 0.34, P = 0.15). There was a significant negative correlation between cerebral FOE and PaCO2 within individuals (n = 14, r = -0.63, P = 0.01), but there was no relationship between individuals (n = 14, r = 0, P = 1). Cerebral FOE was not significantly altered in neonates with either mild anemia or hypotension. There were, however, changes in cerebral FOE when physiological changes occurred over a relatively short period: Cerebral FOE decreased after blood transfusion and increased with decreasing PaCO2. As no change in cerebral FOE was seen during hypotension, it was speculated that cerebral oxygen delivery may have been maintained by cerebral blood flow autoregulation.