<p>Locked-in syndrome (LIS) is a very rare neurologic condition characterized by complete paralysis of all voluntary muscles except for those controlling vertical eye movements and blinking. The individual remains fully conscious but mute and quadriplegic, interacting only through eye movements. We report a case of a 45-year-old female with no significant medical history who presented to the emergency room with drowsiness, unresponsiveness, and excessive snoring. Toxicology was positive for benzodiazepines. Initially in a comatose state requiring intubation and ventilatory support, she was later evaluated by a neurologist who suspected encephalopathy. While initial MRI and EEG were unremarkable, subsequent MR Angiography showed focal restricted diffusion suggestive of infarct, and findings suspicious for viral encephalitis. However, lumbar puncture could not be performed due to her critical condition. During hospitalization, the patient developed Methicillin-resistant Staphylococcus aureus (MRSA) infection, and strict contact precautions were observed. She also suffered an upper gastrointestinal bleed, likely due to drug interactions involving clopidogrel, aspirin, and heparin. This led to a careful rechallenge and dechallenge of anticoagulants and antiplatelets to stabilize the patient. The patient was eventually diagnosed with LIS based on lack of voluntary motor activity except vertical eye movement. On day 18, she was decannulated from the tracheostomy tube and began attempting communication. She was discharged in stable condition after 27 days. This case highlights the diagnostic challenge of LIS, especially in the absence of initial history of drug ingestion, and underscores the importance of thorough neurological assessment. To the best of our knowledge, this is one of the few reported cases of Locked-in Syndrome caused by benzodiazepine poisoning.</p>