We aimed to determine the association between cerebral regional oxygen saturation (rSO₂) trends from cerebral near-infrared spectroscopy (cNIRS) and acute brain injury (ABI) in adult venoarterial extracorporeal membrane oxygenation (VA-ECMO) patients. ABI was defined as intracranial hemorrhage, ischemic stroke, hypoxic ischemic brain injury, or brain death during ECMO. rSO₂ values were collected from left and right cerebral oximetry sensors every hour from ECMO cannulation. Cerebral desaturation was defined as consecutive hours of rSO₂ < 40%. rSO₂ asymmetry was determined by (a) averaging left/right rSO₂ difference over the entire ECMO run; (b) consecutive hours of rSO₂ asymmetry. Sixty-nine VA-ECMO patients (mean age 56 years, 65% male) underwent cNIRS. Eighteen (26%) experienced ABI. When the mean rSO₂ asymmetry was >8% there was significantly increased odds of ABI (aOR = 39.4; 95% CI = 4.1–381.4). Concurrent rSO₂ < 40% and rSO₂ asymmetry >10% for >10 consecutive hours (asymmetric desaturation) was also significantly associated with ABI (aOR = 5.2; 95% CI = 1.2–22.2), but neither criterion alone were. Mean rSO₂ asymmetry>8% exhibited 39% sensitivity and 98% specificity for detecting ABI, with an area under the curve (AUC) of 0.86, and asymmetric desaturation had 33% sensitivity and 88% specificity, with an AUC of 0.72. These trends on NIRS monitoring may help detect ABI in VA-ECMO patients.