ObjectiveTo systematically review the clinical features of chronic fatigue syndrome (CFS) cases with pathogens infection. MethodsWe electronically searched databases including VIP, WanFang Data, CNKI, CBM, PubMed, MEDLINE, EMbase, The Cochrane Library, Web of Science, Elsevier and Google Scholar from 1994 to 2014 for CFS-related studies. Two reviewers independently screened literature and extracted data. Then we systematically reviewed and analyzed the information on demographic characteristics, clinical manifestations, types of infected pathogens, and results of some biochemical examinations. ResultsA total of 84 studies (case reports and case series) involving 2 565 CFS cases from 18 countries were included. The major infected pathogens of included CFS cases were mycoplasma, EB virus, intestinal virus, Bernat rickettsia, human-herpes virus, and Gram-negative intestinal bacteria. Fifty-seven studies reported that there might be associations between the pathogenic infection and CFS pathogenesis. Although there were different types of CFS-related pathogens, almost all the studies inferred that pathogens infection linked with immune dysfunction, which might cause CFS symptoms. ConclusionThere may be associations between the pathogenic infection and CFS pathogenesis.