Burn patients with large burn surface area involvement are at increased risk of infection due to the presence of large wounds, multiple surgeries, prolonged intensive care unit admission, and immunosuppression. Pseudomonas aeruginosa (P. Aeruginosa) is the most commonly isolated organism in this population. Even with frequent infections in the burn population, meningitis and encephalitis are rare, and ventriculitis is exceptional. We report the case of a 66-year-old woman who developed P. Aeruginosa bacteremia during her hospital course, causing secondary meningoencephalitis with ventriculitis. She was admitted for partial and full thickness burns affecting the neck, chest, abdomen, upper medial arms, and bilateral anteromedial thighs for an estimated 20% total body surface area burn. She met sepsis criteria and broad-spectrum antimicrobial coverage was initiated. Magnetic resonance imaging of the brain, performed for altered mental status, revealed meningitis and ventriculitis. Cerebrospinal fluid analysis demonstrated findings consistent with bacterial meningitis, with cultures positive for P. Aeruginosa. Serial neuroimaging with computerized tomography revealed new areas of ischemia concerning for septic emboli. In the presence of altered mental status and fever of unknown origin, workup should remain broad. Even in the presence of another source, it is important to keep an open mind for the rarer intracerebral infection as it requires different management, including urgent evaluation of antibiotic selection and dosing to ensure central nervous system penetration, and neurosurgical evaluation.