BACKGROUND: It has been hypothesised that a link exists between erythrocyte metabolism (particularly redox metabolism) and erythrocyte shape and that both of these are related to erythrocyte deformability. The aim of this research is to confirm the results of earlier studies and to investigate a correlation between erythrocyte morphology and erythrocyte oxidative damage in Chronic Fatigue Syndrome (CFS). METHODS: Reduced glutathione (GSH), malondialdehyde (MDA), methaemoglobin (metHb) and 2,3-diphosphoglyceric acid (2,3-DPG) were measured in patients suffering from CFS and healthy control subjects. Scanning electron microscopic studies of the erythrocytes from both groups were also carried out. RESULTS: There was evidence of oxidative damage in CFS with 2,3-DPG, metHb and MDA significantly increased. The CFS patients in this study also had significantly more stomatocytes in their blood than the normal subjects. CONCLUSIONS: There is a strong likelihood that erythrocyte oxidative damage is the cause of the presence of stomatocytes. The results of this study provide further evidence for the role of free radicals in the pathogenesis of CFS and a link between erythrocyte metabolism and erythrocyte shape.