A 70-year-old immunocompetent male in South Carolina was admitted secondary to altered mental status and headache without focal neurological deficits. Head CT was negative. Lumbar puncture (LP) revealed normal glucose, elevated protein, and lymphocytosis. Opening pressure was 15 cm of H20. CSF lateral flow assay was negative for cryptococcal antigen; CSF cultures showed no growth. The patient rapidly improved on acyclovir and was diagnosed with presumed viral meningitis, as viral PCR and fungal culture were pending at time of discharge. The patient’s condition quickly worsened and the patient returned one day later with right arm weakness and dysarthria. Brain MRI revealed T2/flair signal abnormalities in the left frontal lobe with associated parenchymal enhancement. Repeat LP revealed increasing white blood cell count with a worsening lymphocytosis and decreasing glucose, and opening pressure remained normal. CSF fungal culture from the first admission grew Cryptococcus gattii, and repeated CSF cryptococcal antigen and culture returned positive. The patient was started on IV steroids, induction Amphotericin and Fluconazole, followed by maintenance oral Fluconazole. The patient’s clinical course was complicated by a brainstem lacunar infarction, which led to demise. We present this case of Cryptococcus gattii meningoencephalitis to highlight the risk factors, characteristics, and challenges in diagnosis and treatment of an emerging disease in the Southeastern United States.