This study was designed to evaluate the effect of normothermic partial bypass, or venoarterial extracorporeal membrane oxygenation (ECMO), on cerebral autoregulation. Fourteen newborn lambs, 1–7 d of age, were randomized into two groups: control (ligation of right carotid artery and jugular vein without ECMO; n = 7) and ECMO (ligation with placement on routine venoarterial ECMO at 120–150 mL/kg/min; n = 7). After 1 h of ECMO or stabilization in controls, cerebral autoregulation was evaluated by lowering cerebral perfusion pressure (CPP) by increasing intracranial pressure through infusion of artificial cerebrospinal fluid into the lateral ventricle. Four ranges of CPP were evaluated: 1) baseline, 2) 55–40, 3) 39–25, and 4) < 25 mm Hg. In ECMO animals, cerebral blood flow (CBF) decreased from baseline (39 ± 7 mL/100 g/min) to 23 ± 7 and 12 ± 2 at CPP of 39–25 and < 25 mm Hg. In the control group, CBF was unchanged from baseline (48 ± 11 mL/100 g/min) until CPP was < 25 mm Hg, at which time it decreased to 27 ± 16 mL/100 g/min. Cerebral oxygen consumption decreased from baseline (4.2 ± 1.1 mL/100 g/min) to 4.0 ± 0.7 and 3.2 ± 1.3 mL/100 g/min at CPP of 39–25 and < 25 mm Hg, respectively, in the ECMO group. In the control group, cerebral oxygen consumption was unchanged from baseline (4.2 ± 1.1 mL/100 g/min) until CPP was reduced to < 25 mm Hg (3.2 ± 1.3 mL/100 g/min). When CBF autoregulation was altered, i. e. when total CBF decreased, right-left hemispheric CBF differences were noted in both groups. These findings show that venoarterial ECMO, at flow rates of 120–150 mL/kg/min, alters cerebral autoregulation in healthy newborn lambs and that, if CBF is decreased by an increase in intracranial pressure, carotid artery ligation can result in lower CBF on the ipsilateral side.