Marfan patients report fatigue as a major subjective complaint. We found no studies exploring the subject. The aim of this study was in a strictly defined Marfan population to assess self-reported fatigue, cognitive functions and psychological distress, correlations among them and correlations to visual acuity, joint hypermobility and use of beta-blockers. Sixteen subjects aged 18 - 30 years, fulfilling the Gent criteria, were assessed with the Fatigue Severity Scale, Fatigue Questionnaire, a comprehensive battery of neuropsychological tests and the General Health Questionnaire (GHQ). Self-reported fatigue was comparable with fatigue reported in other severe chronic diseases and disabilities, and was primarily in the mental/psychological domain. Psychological distress was higher than expected compared with the population at large. All neuropsychological test results were within the normal range, except for tests of visuo-motor coordination and speed of information processing. There was a significant inverse correlation between Fatigue Questionnaire ratings and some neuropsychological tests. Fatigue seems to be a serious problem for persons with Marfan syndrome and seems related to some areas of cognitive functioning. We found no overall impairment in cognitive functioning, but slightly reduced speed of information processing. Reduced visuo-motor coordination could be explained by impaired visual acuity.