HSV-1 encephalitis (HSE) is the most common cause of fatal sporadic encephalitis in the United States. HSE in adults is most commonly due to the reactivation of HSV in the central nervous system (CNS) which results in CNS necrosis leading to neurological compromise. The most common symptoms include altered mentation, fever, seizures, and focal neurological deficits. HSE most commonly involves damage to the temporal lobes however can rarely involve other CNS structures such as the brainstem and cerebellum. Immunocompromised status may increase the risk of atypical HSE. HSE involvement of the brainstem, particularly the pons, most commonly cause neuro-ocular and neuro-bulbar deficits. Rarely can HSV brainstem encephalitis cause quadriplegia or locked-in syndrome. We present a case of HSV-1 rhombencephalitis complicated by locked-in syndrome in a patient with CLL.