This study examined the relationships between cerebral fractional oxygen extraction (FOE), mean arterial blood pressure (MABP), left ventricular output (LVO), blood gases, and other physiologic variables in 36 very-low-birth-weight preterm infants during the first 3 d after birth. There was a decrease in cerebral FOE (p = 0.008), and rises in LVO (p < 0.0001) and MABP (p = 0.02) during the 3 d. Between d 1 and 2, cerebral FOE decreased (p = 0.007) and LVO increased (p < 0.0001). There was no relationship between MABP and cerebral FOE. LVO correlated negatively with cerebral FOE on d 1 (p = 0.01), but not on d 2 (p = 0.07). On d 1, median pressure of arterial CO(2) was lower in infants with low LVO (<5(th) centile) and high cerebral FOE (>95(th) centile) than in infants with low LVO (<5(th) centile) but normal cerebral FOE (5(th)-95(th) centile) (p = 0.03). These findings suggest that cerebral FOE was increased only when LVO was low and there was hypocarbia. MABP had no demonstrable effect. It is likely that increased cerebral FOE is a normal physiologic response to maintain an adequate oxygen supply to the cerebral tissues when LVO is low and hypocarbia has caused vasoconstriction. It is possible that the cerebral hemispheres are low-priority vascular beds in the preterm infant, and that the high cerebral FOE is a result of reduced hemispheric blood flow to maintain MABP in the presence of low LVO.