Background: Coffee and caffeine are considered to have beneficial effects in patients with multiple sclerosis (MS), an autoimmune disease of the central nervous system (CNS) that can lead to disability and chronic fatigue.Methods: In the present study the preference in terms of coffee and caffeine consumption in patients with MS was assessed. In total the opinions of 124 MS patients were explored with a questionnaire, which was developed to investigate the consumption behavior and associated beneficial and harmful effects of coffee and caffeine concerning symptoms of fatigue.Results: Our study showed that 37.1% of the included patients experience severe symptoms of fatigue. In our cohort, fatigue was not related to age, type of diagnosis or duration of the disease. The effects of coffee did not differ between MS patients with and without fatigue. Very few side effects linked to coffee consumption were reported, and we could demonstrate that coffee consumption had no negative impact on quality of sleep. A positive effect on everyday life was observed particularly among patients with a mid-level expanded disability status scale (EDSS). The strongest effects of coffee consumption were observed regarding a better ability to concentrate while fulfilling tasks, an expanded attention span and a better structured daily routine.Conclusions: Since coffee showed no severe side effects and in the absence of an effective fatigue therapy, coffee consumption might be a therapeutic approach for selected patients with MS-related fatigue.