A 61-year-old male with a recent diagnosis of pemphigus vulgaris was brought to the emergency department for altered mental status. He had recently started taking prednisone to manage his autoimmune disease and had a progressive decline in his mental status along with decreased oral intake. Evaluation revealed hyperosmolar hyperglycemic state (HHS) and occlusive arterial thrombosis, a rare but known complication of HHS. He was resuscitated aggressively with intravenous fluids, insulin, and heparin and admitted to the intensive care unit. Emergency physicians should remain vigilant for ischemic complications in patients with HHS. Early recognition and treatment can reduce the morbidity and mortality associated with this endocrine emergency.