Cryptococcus neoformans meningoencephalitis was diagnosed as the cause of stupor and generalized seizures in a 2-year-old Cocker Spaniel. Unilateral granulomatous chorioretinitis was observed ophthalmoscopically, and isolation of C neoformans from CSF confirmed the antemortem diagnosis. The dog was euthanatized and necropsied. Multifocal lesions were seen throughout the lungs, nasal turbinates, cerebral cortex, and the optic nerve of each eye. Microscopically, the multifocal lesions were granulomas consisting of lymphocytes, macrophages, plasma cells, and cryptococcal organisms. Infection may have originated in the nasal passages and extended directly through the ethmoid plate into the meninges of the CNS and optic nerves. Although the prognosis is poor in dogs with CNS involvement, various chemotherapeutic agents are available for use by clinicians.