CASE PRESENTATION: A 49-year-old white male with Stage 3C metastatic melanoma presented with altered mental status, fever, palpitations, and diarrhea. Patient was treated with ipilimuab for the melanoma with the most recent dose received 3 weeks ago. He was treated for meningitis with broad spectrum antibiotics, but did not show much clinical improvement, and required mechanical ventilation for worsening mental status and inability to protect his airway. A thorough investigation for infectious and autoimmune causes was negative. He was persistently tachycardic in the 160s and also developed new onset systolic heart failure. Thyroid function studies showed TSH <0.01 micro IU/ml (normal 0.3-4.7), T3 of 22 pg/ml (normal 2.4-4.2), and free T4 level of 5 ng/dl (normal 0.7-1.6). Based on the Burch and Wartofsky scoring system, the patient was diagnosed with thyroid storm most likely due to ipilimumab. He was treated with hydrocortisone equivalent to prednisone 1 mg/kg, propylthiouricil, Lugol's solution, and betablockers, and responded well to the treatment. He was extubated with gradual improvement of his mental status.