Context: Several studies have controversial results regarding the association between Borna disease virus (BDV) and CHRONIC FATIGUE SYNDROME (CFS). The present systematic review and meta-analysis investigated the association between CFS and BDV. Evidence Acquisition: The present study was conducted based on the PRISMA guidelines for systematic review and meta-analysis studies. To avoid bias, all procedures of the study were performed by two researchers independently. A comprehensive search was performed using online databases, including PubMed, Scopus, Embase, PsycINFO, science Direct, Cochrane Library, web of science, and Google scholar using the MeSH keywords until December 12th, 2016. Heterogeneity among studies was evaluated using Cochran’ s Q test I2 Index. Finally, the random effect model was used for combined Odds Ratio (OR) using Review Manger software version 5. 3. 5. Results: Among 9 eligible studies comprising 610 cases and 2176 controls, the total OR for association between BDV and CFS was estimated to be 10. 41 (95% confidence interval [CI]: 4. 24-25. 55, P < 0. 0001). For subgroup analysis by the diagnostic methods (ELISA, RT-PCR, and Western blot), OR was 2. 47 (95% CI: 0. 77-7. 96, P=0. 13), 12. 20 (95% CI: 1. 66-89. 57, P=0. 01), and 28. 36 (95% CI: 3. 76-213. 85, P=0. 001), respectively (test for subgroup differences: P=0. 08; I2=59. 5). Subgroup analysis for BDV and CFS association by antigens and antibodies had an OR of 12. 20 (1. 66, 89. 57) and 8. 20 (3. 32, 20. 22), respectively (test for subgroup differences: P=0. 72; I2=0). Conclusions: This study supports the association between BDV and CFS and shows the role of viral agents in etiology of CFS. Therefore, viral agents may play a role in the etiology of neuropsychiatric disorders.