Introduction: Previously we showed that cardiopulmonary bypass during cardiac surgery is associated with reduced sublingual microcirculatory perfusion and oxygenation. It has been suggested that impaired microcirculatory perfusion may be paralleled by increased heterogeneity of flow in the microvascular bed, possibly leading to arteriovenous shunting. Here we investigated our hypothesis that acute hemodynamic disturbances during extracorporeal circulation indeed lead to microcirculatory heterogeneity with hyperdynamic capillary perfusion and reduced systemic oxygen extraction. Methods: In this single-center prospective observational study, patients undergoing cardiac surgery with (n=18) or without (n=13) cardiopulmonary bypass (CPB) were included. Perioperative microcirculatory perfusion was assessed sublingually with sidestream dark field imaging and recordings were quantified for microcirculatory heterogeneity and hyperdynamic capillary perfusion. The relationship with hemodynamic and oxygenation parameters was analyzed. Results: Microcirculatory heterogeneity index increased substantially after onset of CPB (0.5 [0.0-0.9] to 1.0 [0.3-1.3]; P=0.031) but not during off-pump surgery. Median capillary red blood cell (RBC) velocity increased intraoperatively in the CPB group only (1600 [913-2500 microm/s] versus 380 [190-480 microm/s]; P<0.001), with 31% of capillaries supporting high RBC velocities (>2000 microm/s). Hyperdynamic microcirculatory perfusion was associated with reduced arteriovenous oxygen difference and systemic oxygen consumption during and after CPB. Conclusions: The current study provides the first direct human evidence for a microvascular shunting phenomenon through hyperdynamic capillaries following acute physiological disturbances after onset of cardiopulmonary bypass. The hypothesis of impaired systemic oxygen offloading caused by hyperdynamic capillaries was supported by reduced blood arteriovenous oxygen difference and low systemic oxygen extraction associated with cardiopulmonary bypass.