Necrotizing enterocolitis (NEC) affects 5-10% of very-low-birth-weight infants and remains a leading cause of mortality and long-term morbidity. Preterm infants with NEC, especially those requiring surgery, have higher inflammatory markers in the blood, severe white matter abnormalities on brain imaging, and adverse neurodevelopmental outcomes. This review presents current evidence regarding the clinical factors associated with brain injury in preterm infants with necrotizing enterocolitis needing surgical intervention. Studies that evaluate neuroprotective strategies to prevent brain injury are greatly needed to improve neurodevelopmental outcomes in high-risk preterm infants with NEC.