Clinical outcomes were reviewed for 4 patients with Cryptococcus gattii central nervous system infection who received dexamethasone for the treatment of persisting mental status abnormalities and focal lesions on brain scan despite culture-negative cerebrospinal fluid and the management of intracranial pressure. Favorable clinical responses were observed in 3 patients. Although corticosteroids are not recommended for the treatment of cryptococcal meningitis, these observations suggest that dexamethasone should be further evaluated in this subset of patients.