The present invention relates in a first aspect to a therapeutically effective amount of a stimulator of the soluble guanylate cyclase and/or of an activator of the soluble guanylate cyclase for use in the treatment of chronic fatigue syndrome (CFS) in a patient in need thereof. In a further aspect, the present invention relates to a combination of the stimulator and/or activator of the soluble guanylate cyclase with a B-cell depleting agent in the treatment of chronic fatigue syndrome. In addition, a combination of stimulator and/or activator of the soluble guanylate cyclase with B-Cell depleting agent is described. Said combination may be provided in form of a kit comprising suitably effective dosages of said compounds.