Objective To compare the levels of 21 amino acids in the serum of patients with neuromyelitis optica spectrum disorder（ NMOSD） and myelin oligodendrocyte glycoprotein（ MOG） antibodyassociated disease（ MOGAD）， and explore the correlation between amino acid level differences and neurological disability. Methods From the China National Registry of Neuro-Inflammatory Diseases（ NCT05154370）， 137 patients who were admitted to the Department of Neurological Infection and Immunology of Beijing Tiantan Hospital， Capital Medical University and diagnosed with NMOSD or MOGAD from January 2024 to January 2025 were selected as study subjects， including 92 NMOSD patients and 45 MOGAD patients. The levels of 21 amino acids in the serum of two groups of patients were detected and compared using liquid chromatographymass spectrometry（ LC-MS/MS）. Pearson correlation was used to analyze the correlation between amino acids and the Expanded Disability Status Scale（ EDSS） scores in patients with NMOSD. Results The levels of eight essential amino acids（ leucine， methionine， tryptophan， phenylalanine， lysine， valine， isoleucine， and threonine） in the serum of patients in the NMOSD group were all lower than those in the MOGAD group， with statistically significant differences（ Z/t=3.116， 3.139， 2.683， 2.130， 2.060， 2.411， 2.225， 2.014； all P＜ 0.05）. The levels of four non-essential amino acids（ tyrosine， glutamine， asparagine， and proline） in the serum of patients in the NMOSD group were lower than those in the MOGAD group， and the differences were statistically significant（ t/Z=2.184， 2.463， 2.805， 2.351； all P ＜ 0.05）. The levels of serum tryptophan， valine， and tyrosine in patients with NMOSD were statistically negatively correlated with EDSS scores（ r=-0.318， -0.248， -0.242； all P＜ 0.05）. Conclusions Lower overall amino acid levels are one of the key reasons why patients with NMOSD experience more severe neurological disability than those with MOGAD. Paying attention to the metabolic and nutritional status of patients with NMOSD and supplementing them with essential amino acids play a positive role in improving their condition and halting disease progression.