Background Recently, the neutrophil-lymphocyte ratio (NLR) has become a biomarker for assessing inflammatory stress and prognosis in different diseases. Objective We aimed to conduct a systematic review and meta-analysis to summarize the current evidence on the capacity of the NLR to serve as a biomarker in neuromyelitis optica spectrum disorder (NMOSD). Methods Through a comprehensive systematic search up to December 2021 and using the search terms "neutrophil-to-lymphocyte ratio" and "neuromyelitis optica spectrum disorder" we selected studies evaluating NLR values in NMOSD patients. A meta-analysis was planned, and a narrative synthesis was performed when this was not possible. Subgroup and sensitivity analyses were planned. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach was used to assess certainty of the evidence. Results Six studies were included (1036 patients). A significant increase in the NLR was observed between NMOSD patients and healthy controls with high heterogeneity (MD: 1.04; 95% CI: 0.76; 1.32; I2 = 59%). Regarding NMOSD prognosis, relapse (OR: 1.33 –OR: 2.14) was evaluated as being related to NLR with low certainty. An association with Expanded Disability Status Scale (EDSS) score ≥4 (OR: 1.23 –OR: 1.43) was reported with moderate certainty. An association with the occurrence of lesions on MRI was reported with an OR of 1.52. Conclusion We found the NLR to be useful as a biomarker of NMOSD as it was significantly increased in the patient group compared to the healthy control group with high certainty. Additionally, the NLR was applicable as an indicator of poor prognosis with low to moderate certainty.