Background: Previous studies with a small sample size have not reported metabolic changes in neuromyelitis optica (NMO). Metabolic changes, such as decreased N-acetylaspartate (NAA), are well-established in patients with multiple sclerosis (MS). It remains unknown whether different patterns of metabolic changes occur in NMO and MS. Purpose: To investigate the metabolic changes in normal-appearing white matter (NAWM) in NMO, compared with MS patients and healthy controls (HC), and correlate these changes with clinical disability. Material and Methods: We recruited 27 patients with NMO, 24 patients with MS, and 24 HC. Each participant underwent chemical shift imaging with a 1H-MR spectroscopy operating in a 1.5 T magnetic resonance imaging (MRI) scanner. The absolute concentrations of NAA, choline (Cho), creatine (Cr) as well as the metabolite ratios of NAA/Cr, Cho/Cr, and NAA/Cho were measured and compared among the groups. The correlations between the metabolic concentrations, disease duration, and clinical disability (Expanded Disability Status Scale, EDSS) were further explored. Results: Compared with HC, a mild increase of Cho without significant NAA changes was observed in NMO patients, while both a significant reduction of NAA and an increase of Cho were observed in MS patients. The absolute concentration of NAA and NAA/Cho ratio were significantly decreased in MS patients in a direct comparison with NMO patients. In MS patients, the EDSS was correlated with the NAA/Cr and Cho/Cr ratios. Conclusion: A reduction of NAA was not observed in NMO, implying axonal or neuronal damage may be absent in NAWM for NMO, which is different from MS. A mild increase in Cho was observed in NAWM of NMO patients, suggesting that subtle metabolic changes occur in NMO.