BACKGROUND: Biomarkers that predict disease activity and prognosis should be established for neuromyelitis optica spectrum disorders (NMOSD). In this study, we investigated the association between complement factors and the prognosis of NMOSD. METHODS: We validated laboratory parameters as potential prognostic factors in 34 patients with NMOSD (31 females and 3 males) whose serum was collected at the time of recurrence and who were subsequently followed-up for 3 years without the use of biologics. Ba, sC5b-9, factor H (FH) and haemolytic complement (CH50) were measured as complement factors in the stored sera. Clinical information and cerebrospinal fluid test results were collected from the patients' medical records. This study was approved by the ethics committee of our institution. RESULTS: Disease duration and cerebrospinal fluid protein levels were correlated with the expanded disability status scale at recurrence. sC5b-9 level correlated with the annual relapse rate at 1 year. Furthermore, the sC5b-9 level was significantly different between the groups that relapsed within 1 year and those that did not. At the 3-year follow-up after recurrence, the sC5b-9 and FH levels showed significant differences in the recurrence-free rates between the normal and abnormal groups. CH50 was not useful in predicting prognosis. In individual cases, high sC5b-9 levels and low FH levels were associated with the risk of recurrence. CONCLUSION: Complement values such as sC5b-9 and FH can provide approximate prognostic biomarkers. In the future, it may be possible to determine the course of treatment.