Assessment of cerebral autoregulation is challenging under different hemodynamic conditions during cardiac surgery and must be rapidly calculated in order to optimize mean arterial pressure (MAP). Whether systemic flow during cardiopulmonary bypass impacts the lower limit of cerebral autoregulation (LLA) remains unclear. Forty patients requiring cardiac surgery were included in this randomized crossover study. Patients assigned to the conventional/high blood flow arm received 20 min of conventional cardiopulmonary bypass (CPB) blood flow (2.2 L/min.m⁻²) followed by 20 min of high blood flow (2.8 L/min.m⁻²), both during aortic cross clamping. Patients assigned to the high/conventional arm received the same flows but in reverse order. During each 20-minute period, MAP was gradually increased from 40 to 90 mmHg, while PaCO₂, hematocrit, depth of anesthesia, central temperature and arterial oxygen tension were kept constant. Continuous cerebral blood flow velocities of the middle cerebral artery (Fv) were monitored using transcranial doppler. Cerebral autoregulation was calculated using a Pearson’s correlation coefficient (Mean flow index, Mxa) between the MAP and Fv. Mxa values were then plotted across MAP ranges. The LLA was defined as the corresponding MAP value when Mxa initially decreased and crossed the threshold value of 0.4. A mixed model, including the LLA as the dependent variable, the CPB flow and period as fixed effects and patients as a random effect was used to compare conventional and high CPB flows. Thirty-seven patients were analyzed. The LLA mean difference between groups, adjusted on the period, was − 2.8 (SE 2.4) mmHg with 95% CI [-7.8, + 2.1 mmHg], p = 0.2538). 24% of patients presented an LLA < 65 mmHg during the conventional CPB flow phase versus 35% during the high CPB flow phase. Increasing the cardiopulmonary pump flow did not decrease the LLA during cardiac surgery.