Background. Neurocognitive deficits after open heart operations have been correlated to jugular venous oxygen desaturation on rewarming from hypothermic cardiopulmonary bypass (CPB). Using a porcine model, we looked for evidence of cerebral hypoxia by magnetic resonance imaging during CPB. Brain oxygenation was assessed by T2∗-weighted imaging, based on the blood oxygenation level-dependent effect (decreased T2∗-weighted signal intensity with increased tissue concentrations of deoxyhemoglobin). Methods. Pigs were placed on normothermic CPB, then cooled to 28°C for 2 hours of hypothermic CPB, then rewarmed to baseline temperature. T2∗-weighted imaging was undertaken before CPB, during normothermic CPB, at 30-minute intervals during hypothermic CPB, after rewarming, and then 15 minutes after death. Imaging was with a Bruker 7.0 Tesla, 40-cm bore magnetic resonance scanner with actively shielded gradient coils. Regions of interest from the magnetic resonance images were analyzed to identify parenchymal hypoxia and correlated with jugular venous oxygen saturation. Post-hoc fuzzy clustering analysis was used to examine spatially distributed regions of interest whose pixels followed similar time courses. Attention was paid to pixels showing decreased T2∗ signal intensity over time. Results. T2∗ signal intensity decreased with rewarming and in five of seven experiments correlated with the decrease in jugular venous oxygen saturation. T2∗ imaging with fuzzy clustering analysis revealed two diffusely distributed pixel groups during CPB. One large group of pixels (50% ± 13% of total pixel count) showed increased T2∗ signal intensity (well-oxygenated tissue) during hypothermia, with decreased intensity on rewarming. Changes in a second group of pixels (34% ± 8% of total pixel count) showed a progressive decrease in T2∗ signal intensity, independent of temperature, suggestive of increased brain hypoxia during CPB. Conclusions. Decreased T2∗ signal intensity in a diffuse spatial distribution indicates that a large proportion of cerebral parenchyma is hypoxic (evidenced by an increased proportion of tissue deoxyhemoglobin) during CPB in this porcine model. Neuronal damage secondary to parenchymal hypoxia may explain the postoperative neuropsychological dysfunction after cardiac operations.