Chronic fatigue syndrome (CFS) is characterized by severe fatigue, lasting for at least 6 months, for which no somatic explanation can be found. Because hyperventilation can produce substantial fatigue, it seems worthwhile to investigate the relationship between it and CFS. It might be hypothesized that hyperventilation plays a causal or perpetuating role in CFS. CFS patients, non-CFS patients known to experience hyperventilation, and healthy controls were compared on complaints of fatigue and hyperventilation. CFS patients and non-CFS patients known to experience hyperventilation offered substantial complaints of fatigue and hyperventilation, both to a similar degree. Physiological evidence of hyperventilation was found significantly more often in CFS patients than in healthy controls. However, no significant differences between CFS patients with and CFS patients without hyperventilation were found on severity of fatigue, impairment, number of complaints, activity level, psychopathology, and depression. It is concluded that hyperventilation in CFS should probably be regarded as an epiphenomenon.