The present invention relates in a first aspect to a B-cell depleting anti-CD20 antibody or a CD20-binding antibodyfragment thereof for the treatment of chronic fatigue syndrome and myalgicencephalomyelitis. In particular, the present inventionrelates to the use of anti-CD20 monoclonal antibodies or fragments thereofwhich are preferably humanized for the treatment ofchronic fatigue syndrome/myalgic encephalomyelitis in a subject afflicted withsaid disease.