Background: Comorbidity may influence clinical aspects of neuromyelitis optica spectrum disorder (NMOSD). We estimated the prevalence of comorbidities to assess their association with outcomes. Methods: This retrospective study assessed records of NMOSD patients from 2008 to 2019, categorizing comorbidities into three groups: somatic, psychiatric and autoimmune. Severity of disease was evaluated by the Expanded Disability Status Scale, progression index (PI) and annualized relapse rate. The frequency of comorbidities was compared between anti-aquaporin 4 antibody (AQP4-IgG) seropositive and seronegative patients. Results: A total of 67 NMOSD patients were enrolled. Thirty-five (52.2%) patients reported at least one comorbidity. In total, 44 comorbidities were found, of which 24 occurred prior to NMOSD onset: 29 somatic, 13 psychiatric and 2 autoimmune entities. The most common comorbidities were anxiety disorders 7/67 (10.4%), followed by migraine 6/67 (8.9%) major depression disorder 6/67 (8.9%), iron deficiency anemia 8/54 (14.8%), and non-autoimmune hypothyroidism 4/67 (6.0%). Psychiatric comorbidities associated with PI in unadjusted (OR=0.538, 95% CI=0.141, 0.935, P=0.009) and adjusted models (OR=0.386, 95% CI=0.022, 0.751, P=0.038). A significantly higher frequency of psychiatric comorbidities was observed in the AQP4-IgG positive patients (P=0.031). Conclusion: Half of the patients had comorbidities, suggesting screening for comorbidity as part of NMOSD care. The psychiatric comorbidities had impact on clinical outcome.