An adult female sea otter housed for 5 years in an outdoor habitat in an aquarium developed signs of neurologic disease. Bilateral caudal paresis was evident initially and other neurologic signs consistent with CNS disease developed rapidly. Diagnostic work-up included CBC, serum biochemical analyses, determination of serum antibody titers, radiography of the vertebral column, CSF analysis, muscle biopsy, computed tomography of the brain, and assays for mercury, lead, and thiamine. A tentative diagnosis of encephalitis caused by a Sarcocystis neurona-like organism was made on the basis of detection of CSF antibodies by use of Western blot analysis. Response to treatment was not satisfactory and the sea otter was euthanatized. Immunohistochemical staining revealed S neurona-like organisms within foci of inflammation in the brain and spinal cord. This report provides evidence that, for sea otters, there may be a mode of transmission of an S neurona-like organism that does not involve opossums.