Cerebral autoregulation (CA) maintains cerebral blood flow (CBF) constant over a wide range of perfusion pressures (MAP). However, arterial PCO2 (PETCO2) may modify CBF if brain metabolism and total oxygen consumption (VO2) are modified. During exercise MAP, VO2 and VCO2 are increased and may affect CBF. Female (13) and male (9) subjects completed a CO2 sensitivity test at rest and a graded exercise treadmill test. Heart rate (HR), MAP, ventilation (VE) and CBF velocity (CBFV) were measured in both tests. During rest CBFV (45%) and VE (221%) increased linearly with PETCO2 (58%). During exercise CBFV increased (31%) from 61 ± 16 cm/s to 78 ± 16 cm/s at 80% of VO2max. Once above the ventilatory threshold, CBFV decreased to 65 ± 16 cm/s at 100% VO2max. The changes in CBFV paralleled the changes in PETCO2 (36 ± 5 to 46 ± 6 to 36 ± 6 mmHg), despite a linear increase in MAP with VO2. Multiple linear regression indicated that PETCO2 was contributing more to CBFV than MAP (CBFV = 5.001 + (0.759 * PETCO2) + (0.313 * MAP)). During exercise CA did not maintain CBFV and PETCO2 strongly influenced it, thus ventilatory regulation (PETCO2) in exercise is critical in determining CBF. Resting CO2 sensitivity did not predict exercise PETCO2. Regulation of PETCO2 during exercise may explain the differences in CBF among individuals or conditions. One example may be the dysregulation of CBF in post concussion syndrome patients.