Background: The disruption of the blood-brain barrier (BBB) is common in patients with neuromyelitis optica spectrum disorder (NMOSD), causing pro-inflammatory immune cells to migrate into the central nervous system (CNS) and active demyelinating lesions. Albumin quotient is commonly used as an indicator for BBB permeability or dysfunction, but its potential clinical value in NMOSD treatment has never been explored. The present study investigated the differences in the albumin quotient level among NMOSD patients with different antibodies (AQP4-IgG and MOG-IgG) and the relationship between the albumin quotient and neurological dysfunction. Methods: We retrospectively collected data from 141 patients with NMOSD (104 with AQP4-IgG and 37 with MOG-IgG) and reviewed their clinical features and albumin quotient levels. Results: The percentage of patients with an abnormal albumin quotient was significantly higher in the MOG-IgG group than in the AQP4-IgG group (48.6% vs 27.9%, P = 0.026); albumin quotient levels in the AQP4-IgGpositive group were similar to those in the MOG-IgG groups (5.65 vs 5.8, P = 0.23). Among those with an abnormal quotient, no differences in the proportions of severe neurological disability across treatment were found between patients with AQP4-IgG and those with MOG-IgG (pre-treatment: AQP4-IgG group vs MOG-IgG group: 58.6% vs 38.9%, P = 0.24; post-treatment: AQP4-IgG group vs MOG-IgG group: 31.0% vs 22.2%, P = 0.74). Conclusions: The BBB breakdown in NMOSD patients with MOG-IgG may be more common than in those with AQP4-IgG. AQP4-IgG-positive patients and MOG-IgG-positive patients with severe neurological disability tend to exhibit similar disruptions to the BBB.