Objective: Aim of this study was to evaluate the potential for cerebral protection by using selective cerebral perfusion (SCP) during controlled hypoperfusion and hypothermia as required for the correction of complex congenital cardiac defects. Methods: 15 piglets (7-10kg) received cardiopulmonary bypass at 25°C for 90min of cardioplegic cardiac arrest. SCP was performed via the right common carotid artery. Brain perfusion 1ml/g/min, 0.5ml/g/min, 0.25ml/g/min were evaluated. Clinical parameters and tissue oxygenation index (TOI) were registered online until 3 hours of reperfusion. Brain ischemia was quantified using immunohistological analyses for heat shock protein (HSP70) and apoptosis inducing factor (AIF) on sections of the hippocampus. Results: Intracranial pressure remained stable throughout the study. Hemodynamic parameters, blood gas and lactate measurements were within the normal range until the end of the study. TOI was moderately reduced, HSP70 immunopositivity and AIF immunopositive nuclei significantly increased after extensive hypoperfusion. Conclusions: Regular flow unilateral SCP as well as moderate hypoperfusion are safe. Extensive hypoperfusion (25% of regular blood flow) leads to progressive initiation of apoptosis indicating cerebral ischemia.