Congenital heart disease often requires early surgical intervention. Cardiopulmonary bypass (CPB) is a standard procedure, but infants undergoing CPB show an increased risk of postoperative white matter injury. These injuries are associated with adverse neurodevelopmental outcomes, yet the underlying mechanisms remain poorly understood. MR imaging offers unique opportunities to study cerebral perfusion and metabolism in vivo but has not previously been feasible during CPB with a heart-lung machine (HLM) in close proximity to the patient and the MR scanner, respectively, because conventional HLMs interfere with scanner operation. To address this limitation, we developed an MR-conditional HLM and evaluated it in an in vivo piglet model, which closely mimics the neonatal brain and circulation. Unlike conventional systems, our MR-conditional roller pump can be positioned directly inside the scanner bore without compromising imaging quality or pump performance. Four trials were conducted, in which piglets were cannulated and maintained on CPB inside the MR scanner. During CPB, cooling, rewarming, and unilateral carotid clamping were performed while repeatedly acquiring MR data on flow, diffusion, perfusion, and metabolism. Crucial brain structures—including the basal ganglia, hippocampus, and internal capsule—were consistently visualized without artifacts, and no disturbances occurred in pump operation or monitoring signals. The MR scans revealed flow-related changes and a progressive increase in lactate, suggesting the onset of metabolic stress under hypoperfusion. These results demonstrate the technical feasibility of performing CPB within the MR scanner using an MR-conditional HLM. Although not sufficient to identify specific mechanisms of brain injury, this platform provides a unique foundation for mechanistic studies in relevant large-animal models. In the future, such an approach could help identify early markers of cerebral vulnerability, improve the safety of pediatric cardiac surgery, and inform the development of neuroprotective strategies for CPB and extracorporeal membrane oxygenation patients.