Withdrawal and infusion of blood via umbilical catheters can affect cerebral blood flow in preterm infants. We compared the effects on cerebral perfusion of 3 ml/kg blood withdrawal and infusion via umbilical arterial (UAC) and venous (UVC) catheters in 16 infants ≤32 weeks gestation, age <24 h, on mechanical ventilation. Near infrared spectroscopy was used to monitor changes in cerebral oxy- and deoxyhemoglobin, total cerebral hemoglobin (an index of cerebral blood volume; CBV) and HbD (an index of cerebral intravascular oxygenation). In 10 infants the study was repeated 1 h after intravenous administration of 10 mg/kg ibuprofen as prophylaxis against PDA. Withdrawal and infusion via the UVC caused significant MABP and concordant HbD and CBV changes. Smaller modifications were seen following blood withdrawal and infusion via the UAC. Ibuprofen attenuated cerebral hemodynamic changes associated with withdrawal, but not infusion, from UAC and UVC.