Abstract Background: Aquaporin-4 antibody–positive neuromyelitis optica spectrum disorder (AQP4-IgG NMOSD) requires lifelong immunosuppression to prevent relapses and disability. However, long-term treatment can increase the risk of severe and opportunistic infections, which can lead to hospitalisation and death. Objectives: To describe severe infections in AQP4-IgG NMOSD, their outcomes and risk factors, to inform safer long-term management.