Background: Chronic Fatigue Syndrome (CFS) is a complex illness with different clinical definition, etiological models and treatments. A lot of studies have focused on the concomitance with herpesviridae infections, especially Epstein-Barr Virus (EBV).

We report a clinical case highlighting the correlation between chronic EBV infection and CFS.

Results: The patient met the CDC criteria for the diagnosis of CFS and presented a high level of EBV-DNA in blood.

Conclusions: Although some studies suggest that subjects with viral infections are not more likely to develop CFS than controls, the possible connection between EBV and CFS remains unclear.

EBV-DNA shows the presence of an actively replicating virus, which is known to be associated with several cancers. Whether its replication is the cause or the consequence of CSF needs further investigations.