A 22-year-old African woman developed acute behavioural change, against a background of sickle cell disease with strokes requiring a ventriculoperitoneal shunt. She alternated between mutism with prolonged staring and posturing, and a state of agitation with elation and echolalia. Cerebrospinal fluid (CSF) protein was elevated and electroencephalogram showed mild slowing with bitemporal slow and sharp waves. We suspected catatonia secondary to possible autoimmune encephalitis but her condition persisted despite intravenous methylprednisolone. After identifying a positive serum anti-gamma-aminobutyric acid-A (GABA_A) antibody, treatment with intravenous immunoglobulin, oral corticosteroids and rituximab led to gradual improvement. Patients with catatonia may show reduced GABA_A receptor density and there are two other reports of catatonia with anti-GABA_A antibodies. This patient’s treatment response supports the antibody’s causative role.