Chronic fatigue syndrome (CFS) is an illness characterized by persistent and relapsing fatigue, often accompanied by numerous symptoms involving various systems of whole body. The etiology of CFS remains unclear. Literature reported whether the concentrations of the essential fatty acids in red cell membranes of CFS patients were decreased is controversial. In our study, Forty-two patients who fulfilled the diagnostic criteria defined by Centers for Disease Control and Prevention (CDC). Thirty-seven age- and sex-matched controls were selected from healthy medical staffs and volunteers. After lipid analysis, we found that the levels of the arachidonic acid (ARA) and docosahexanoic acid (DHA) were decreased in patients suffered from CFS. However, the levels of the palmitic acid and oleic acid were increased. We speculated that there are two possible mechanisms-one of which is that oxidative stress has led to an excessive oxidation and resulting in the above fatty acids. Alternatively, insufficiency of ingestion of fatty acids might not be the major cause.