Abstract Disclosure: R. Kalas: None. V. Manohar: None. N.S. Bapat: None. Y. Kim: None. Myxedema coma is a rare medical emergency that occurs in severe hypothyroidism with a mortality rate reaching 60%. The hallmarks include depressed mental status and hypothermia, but hypotension, hyponatremia, bradycardia, and hypoventilation can also occur. This complication can occur in patients with a longstanding history of severe hypothyroidism especially when precipitated by an acute event such as infection, myocardial infarction, or surgery. Prompt recognition and treatment of the condition is important to prevent fatal outcomes. We present a case of myxedema coma in the setting of COVID-19 infection and nonadherence to medication. A 91-year-old woman with history of hypothyroidism, hypertension, coronary artery disease, cardiomyopathy, and chronic obstructive pulmonary disease presented with dyspnea. Her home medications included levothyroxine 75 mcg daily, which she reported not taking for at least 3 weeks. Vital signs revealed a normal heart rate and blood pressure of 84 beats/min and 137/78 mmHg, but the patient was hypothermic to 35.7 °C. On exam, she was somnolent. Labs were notable for markedly elevated TSH level of 111 (0.380 - 4.700 uIU/mL), low free T4 level of 0.57 (0.93 - 1.70 ng/dL), random cortisol level of 25.5 (6.2-18.4 ug/dL), and positive SARS-COV-2 PCR test. Chest x-ray revealed bilateral lower lung parenchymal consolidations and arterial blood gas revealed a pH of 7.29 and pCO2 of 52.5 (35-45 mm Hg), indicating hypercapnia. She was treated for COVID pneumonia and given concern for COVID induced myxedema coma she was given IV levothyroxine 100 mcg for 2 days, after which the patient’s hypothermia and somnolence improved, with an improved repeat free T4 level 0.87 ng/dL. She was subsequently transitioned to oral levothyroxine 112 mcg daily and discharged after improvement of her COVID symptoms. Myxedema coma is a rare complication of decompensated hypothyroidism, frequently triggered by an infection. Thyroid hormone plays an important role in regulating both the innate and adaptive immune systems. As a result, individuals with hypothyroidism are at increased risk of acquiring infections, which can further lead to myxedema coma. COVID-19 infection has been associated with thyrotoxicosis, thyroiditis and hypothyroidism. Given the associated high mortality rate, regardless of the underlying precipitant, prompt diagnosis and early administration of thyroid hormone replacement therapy is crucial to improve outcomes. Presentation: 6/3/2024