Autoregulation is a vital protective mechanism that maintains cerebral blood flow stable as cerebral perfusion pressure changes. We contrasted cerebral autoregulation across sleep-wake states as little is known about its effectiveness during sleep. Newborn lambs (n = 9) were instrumented to measure cerebral blood flow (flow probe on the superior sagittal sinus) and cerebral perfusion pressure, then studied during Active Sleep (AS), Quiet Sleep (QS) and Quiet Wakefulness (QW). We generated cerebral autoregulation curves by lowering cerebral perfusion pressure by inflating an occluder cuff around the brachiocephalic artery. Baseline cerebral blood flow was higher (P<0.05) and cerebral vascular resistance lower (P<0.05) in AS than in QW (76 ± 8% and 133 ± 15% respectively of the AS value, mean ± SD) and in QS (66 ± 11% and 158 ± 30%). The autoregulation curve in AS differed from that in QS and QW in three key respects: firstly, the plateau was elevated relative to QS and QW (P<0.05); secondly, the lower limit of the curve (breakpoint) was higher (P<0.05) in AS (50 mmHg) than QS (45 mmHg); and thirdly, the slope of the descending limb below the breakpoint was greater (P<0.05) in AS than QS (56% of AS) or QW (56% of AS). Although autoregulation functions in AS, the higher breakpoint and greater slope of the descending limb may place the brain at risk for vascular compromise should hypotension occur.