Low cerebral blood flow (CBF) states have been demonstrated in children early after traumatic brain injury (TBI), and have been correlated with poorer outcomes. Cerebral perfusion pressure (CPP) support following severe TBI is commonly implemented to correct cerebral hypoperfusion, but the efficacy of various vasopressors has not been determined. Sixteen 4-week-old female swine underwent nonimpact inertial brain injury in the sagittal plane. Intraparenchymal monitors were placed to measure intracranial pressure (ICP), CBF, brain tissue oxygen tension (PbtO2), and cerebral microdialysis 30<min to 6<h post-injury. One hour after injury, animals were randomized to receive either phenylephrine (PE) or norepinephrine (NE) infusions titrated to a CPP >70<mm Hg for 5<h. Animals were euthanized 6<h post-TBI, and brains were fixed and stained to assess regions of cell and axonal injury. After initiation of CPP augmentation with NE or PE infusions, there were no differences in ICP between the groups or over time. Animals receiving NE had higher PbtO2 than those receiving PE (29.6±10.2 vs. 19.6±6.4 torr at 6<h post-injury, p<0.05). CBF increased similarly in both the NE and PE groups. CPP support with PE resulted in a greater reduction in metabolic crisis than with NE (lactate/pyruvate ratio 16.7±2.4 vs. 42.7±10.2 at 6<h post-injury, p<0.05). Augmentation of CPP to 70<mm Hg with PE resulted in significantly smaller cell injury volumes at 6<h post-injury than CPP support with NE (0.4% vs. 1.4%, p<0.05). Despite similar increases in CBF, CPP support with NE resulted in greater brain tissue oxygenation and hypoxic-ischemic injury than CPP support with PE. Future clinical studies comparing the effectiveness of various vasopressors for CPP support are warranted.