To investigate the factors influencing the degree of disability in patients with neuromyelitis optica spectrum disorder (NMOSD) and provide evidence for disease monitoring and clinical intervention.Eighty-four patients with NMOSD at Xuanwu Hospital Capital Medical University were enrolled in this retrospective study. Before treatment, blood was collected from all patients, and their expanded disability status scores were assessed.Of the 84 patients assessed, 66 (78.57%) had an expanded disability status scale score < 7, and 18 (21.43%) had scores ≥ 7. The univariate analysis showed that the total bilirubin (TBil), cerebrospinal fluid albumin (CSF ALB), cerebrospinal fluid immunoglobulin G (CSF IgG), QALB, and QIgG levels in the group with scores ≥ 7 were significantly different from those with scores < 7 (P < 0.05). In addition, Spearman's correlation analysis showed a significant correlation between ALB and expanded disability status scores in patients with NMOSD (P < 0.05), and the multivariate logistic regression analysis showed that TBil was an independent factor influencing the degree of disability in patients with NMOSD (P < 0.05). The receiver operating characteristic curve was constructed using TBil values; the area under the curve of TBil was 0.729 (P < 0.01), and the best cut-off value was 11.015 g/L. Its sensitivity in predicting the severity of disability in NMOSD patients was 51.5% while its specificity was 88.9%.TBil is an independent factor that influences the severity of disability in patients with NMOSD. In addition, ALB is closely related to NMOSD severity, and some factors associated with the BBB are significantly increased in severely disabled NMOSD patients.© 2023. BioMed Central Ltd., part of Springer Nature.