Background and Objective: Plasma homocysteine (Hcy) levels have been investigated among patients with multiple sclerosis (MS). However, the changes in Hcy levels and the association between Hcy levels and inflammatory/immune/cerebrospinal fluid (CSF) parameters in neuromyelitis optica spectrum disorder (NMOSD) patients have not been investigated yet. Methods: Case data were collected from 97 acute-phase NMOSD patients and 39 stable-phase NMOSD patients. Patients in the acute phase were divided into 2 groups based on the EDSS score with cutoff equal to 4. Hcy levels, immunoglobulins (Ig) A, G, and M, complement 3 and 4, CH50, C-reactive protein, erythrocyte sedimentation rate (ESR), and CSF examination including white blood cells and total protein were determined. Results: No significant differences in Hcy levels are observed between acute-phase and stable-phase NMOSD patients. Hcy and ESR levels were significantly higher in acute-phase NMOSD patients with EDSS score ≥4. Besides, EDSS is positively correlated with Hcy level, ESR, 1/aquaporin-4 titer and Hcy level is negatively correlated with IgM in acute-phase NMOSD patients. Conclusion: Elevated plasma Hcy has the potential to affect the pathogenesis or progression of NMOSD.