Neuromyelitis optica (NMO) is a rare inflammatory disorder of the central nervous system characterized by optic neuritis and myelitis. NMO may rarely be accompanied by systemic autoimmune disease including systemic lupus erythematosus (SLE). This immunological overlap may reflect the predisposition of patients with NMO to systemic autoimmunity. We report a young female with relapsing NMO and SLE. The patient was seropositive for anti-aquaporin-4 autoantibody, a highly sensitive and specific marker for NMO. Our case highlights the importance of testing for the anti-aquaporin-4 autoantibody in the case of relapsing myelitis or optic neuritis in patients with SLE for making correct diagnosis and choosing the appropriate management.