Background The identification of biomarkers able to improve the differential diagnosis between multiple sclerosis (MS) and neuromyelitis optica (NMO) is challenging because of a different prognosis and response to treatment. Growing evidence indicates that brain and CSF N-acetyl aspartate (NAA) concentration is a useful marker for characterising different phases of axonal pathology in demyelinating diseases, and preliminary studies suggest that increased serum NAA levels may be a telltale sign of acute neuronal damage or defective NAA metabolism in oligodendrocytes. Objective To evaluate whether serum and CSF NAA concentration differs in patients with MS and NMO. Design Observational, multicentre, prospective, cross sectional study. Methods Serum samples were collected from 48 relapsingeremitting MS, 32 NMO and 76 age matched healthy controls. Coeval CSF samples were available for all MS and for 8/32 NMO patients. NAA was measured in serum and CSF by liquid chromatography-mass spectrometry. Results MS patients showed higher serum and CSF NAA levels than NMO patients, and higher serum NAA levels than healthy controls (p