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Introduction: Serotonin Syndrome (SS) is an under recognized entity which can be life threatening if not recognized early. It is a clinical diagnosis that requires high vigilance. Thorough medication reconciliation is critical, especially when considering non-prescription agents. SS can occur by overuse of a single agent, drug-drug interactions between two or more serotonergic agents. We present a case of serotonin syndrome likely triggered by ondansetron and excessive supplement use of creatine. Description: A 21-year-old male with history of ankylosing spondylitis on Adalimumab for one year presented with unresponsiveness after several days of nausea, vomiting, and headache. He was evaluated at an urgent care and discharge with ketorolac and a prescription for ondansetron. The patient was found obtunded with abrasions. He was febrile (38.9°C), white blood cell count of 24.9K/uL, Sodium 113 mmol/L, and Creatinine Kinase 18,000 U/L. Pupils were mildly dilated. CNS Imaging was unremarkable. He was intubated for airway protection and started on empiric meningitis coverage. A CSF studies showed lymphocytic pleocytosis (WBC 121, protein 117 mg/dL) and a meningitis panel, tick borne panel was all negative. Continuous EEG monitoring was unrevealing. On hospital day one, he received Buspar and Demerol for shivering which made shivering worse with further elevated fever spikes. His bilateral ankle clonus raised concern for serotonin syndrome. Collateral history revealed ondansetron ingestion and excess daily use of creatine for muscle building. He was treated with Lorazepam and Dexmedetomidine. Cyproheptadine was initiated with clinical improvement. Inadvertent re-exposure to ondansetron caused symptom recurrence. Patient was safely discharged home. Discussion: Serotonin syndrome can result from excessive serotonergic activity, even with agents like ondansetron. Creatine has been shown to affect serotonin metabolism and receptor activity in animal models, potentially exacerbating the risk. This underscores the importance of inquiring about supplement use during hospital admission. This case illustrates the importance of thorough history-taking and exam and awareness of drug-induced neurologic syndromes in critically ill patients. Early recognition of serotonin syndrome can significantly alter outcomes.