Abstract: Objective To investigate the serum neurofilament light chain (sNFL) levels in patients with neuromyelitis optica spectrum disorder (NMOSD), and to analyze the correlation between the sNFL levels and severity of disease. Methods Forty-two patients with acute phase of NMOSD hospitalized in the first affiliated hospital of Bengbu medical college were enrolled as the NMOSD group from July 2015 to December 2018, and 42 healthy subjects as the normal control group during the same period. Extended disability status scale (EDSS) was used to evaluate the severity of disease with the NMOSD group, and the levels of sNFL were detected with electrochemiluminescence immunoassay (ECLIA). The sNFL levels of NMOSD group and control group, and the sNFL levels of different subtypes of NMOSD were compared. Simple linear regression was used to analyze the correlation between the sNFL levels and the EDSS scores. Results The sNFL level [(81.69±35.49) pg/mL] in the NMOSD group was significantly higher than that in the normal control group [(16.00±5.61) pg/mL], and the difference was statistically significant (t'=11.848, P<0.001). The sNFL level [109.86±31.45)pg/mL] in the AQP4-Ab (+) group was significantly higher than that in the AQP4-Ab(-) group [(67.61±28.62)pg/mL], and the difference was statistically significant (t=4.365, P<0.001). The sNFL level of NMOSD group was positively correlated with the EDSS score (t=9.108, P<0.001). Conclusion The level of sNFL increased in the acute phase of NMOSD is positively correlated with the severity of the disease.