Purpose <p>In patients with hemorrhagic shock and an intracranial space occupying lesion (SOL), brain perfusion is severely compromised due to raised intracranial pressure (rICP), significantly worsening outcomes. This study aims to develop a swine model of a SOL with rICP and shock and characterize the effect on brain perfusion.</p> Methods <p>Ten male swine were divided into two groups– normal ICP (nICP) and rICP. rICP animals had an intracranial Fogarty balloon catheter inserted, which was infused with saline to simulate a SOL. Animals underwent hemorrhage to systolic blood pressures (SBP) of 60, 40, and 20mmHg. Cerebral blood flow (CBF) and cerebral blood volume (CBV) were measured using CT perfusion.</p> Results <p>The CBF/Mean arterial pressure (MAP) and CBV/MAP curves were modeled using non-linear regression, with both groups demonstrating a sigmoid relation. In both the CBF/MAP and CBV/MAP curves, animals with rICP had loss of autoregulation at a higher MAP compared to nICP. The curves were an excellent fit for CBF (nICP R² = 0.95; rICP R² = 0.77) and CBV (nICP R² = 0.96; rICP R² = 0.78).</p> Conclusions <p>This study aids in quantifying the compounding insult of raised ICP and hemorrhage with regard to brain perfusion. Raised ICP results in autoregulatory failure at a higher MAP compared to animals with nICP. These results can help inform future studies that should be aimed at evaluating novel interventions for this complex clinical scenario.</p>