Abstract Complement is thought to play a pivotal role in neuromyelitis optica (NMO) pathogenesis. Anaphylatoxins (C3a, C4a, and C5a), produced in complement activation, have proinflammatory potential, and thereby may play an important role. We measured concentrations of anaphylatoxins in CSF and sera, obtained from patients with NMO (n = 15), multiple sclerosis (MS) (n = 15), and other neurological disease (OND) (n = 12), and evaluated their clinical implications. The CSF–C5a levels were elevated significantly in NMO patients, especially in patients with multiple enhanced lesions on MRI. The CSF–C5a levels correlated with the severity of exacerbation. Our results may provide a rationale for anti-complement therapies of NMO.