Background: The aims of this work were (1) to compare cerebral oxygenation-perfusion (COP), central hemodynamics, and peak oxygen uptake (V˙o2peak) in heart transplant recipients (HTRs) vs age-matched healthy controls (AMHCs) during exercise and recovery and (2) to study the relationships between COP, central hemodynamics, and V˙o2peak in HTRs and AMHCs. Methods: Twenty-six HTRs (3 women) and 27 AMHCs (5 women) were recruited. Maximal cardiopulmonary function (gas exchange analysis), cardiac hemodynamics (impedance cardiography), and left frontal COP (near-infrared spectroscopy) were measured continuously during and after a maximal ergocycle (Ergoline 800S, Bitz, Germany) test. Results: Compared with AMHCs, HTRs had lower V˙o2peak, maximal cardiac index (CImax), and maximal ventilatory variables (P < 0.05). COP was lower during exercise (oxyhemoglobin [$δ$O2Hb], 50% and 75% of V˙O2peak, total hemoglobin [$δ$tHb], 100% of V˙O2peak; P < 0.05), and recovery in HTRs ($δ$O2Hb, minutes 2-5; $δ$tHb, minutes 1-5; P < 0.05) compared with AMHCs. End-tidal pressure of CO2 was lower during exercise compared with that in AMHCs (P < 0.0001). In HTRs, CImax was positively correlated with exercise cerebral hemodynamics (R = 0.54-0.60; P < 0.01). Conclusions: In HTRs, COP was reduced during exercise and recovery compared with that in AMHCs, potentially because of a combination of blunted cerebral vasodilation by CO2, cerebrovascular dysfunction, reduced cardiac function, and medication. The impaired V˙O2peak observed in HTRs was mainly caused by reduced maximal ventilation and CI. In HTRs, COP is impaired and is correlated with cardiac function, potentially impacting cognitive function. Therefore, we need to study which interventions (eg, exercise training) are most effective for improving or normalizing (or both) COP during and after exercise in HTRs.