Background: In multiple sclerosis (MS) patients, symptoms of anxiety, depression, pain, and cognitive impairment are highly prevalent and contribute to lower wellbeing. As these physical and psychological symptoms of distress often stay unnoticed, regular screening could offer possibilities to identify and refer impaired patients to appropriate care. Objective: The aim of our study was to pilot a new computer-based method in 43 MS patients to efficiently screen for a variety of psychological and physical symptoms of distress. Methods: Data on feasibility and psychological and physical distress (anxiety, depression, fatigue, physical disability, cognitive functioning) were collected via a touch screen computer. Referral to psychosocial care and rehabilitation was retrospectively checked. Results: The results demonstrated that most patients (35/40, 88%) considered the screening meaningful and the system easily usable (37/40, 93%). Average completion time of the screening was below 8 minutes. Many patients (35/40, 88%) had elevated distress levels, of whom the majority was referred. Conclusions: These findings imply that computer-based screening for MS-related distress incorporated in clinical care is feasible and aids to identify psychological or physical needs. A randomized controlled trial with follow-up should address whether this screening method could be more effective than routine care, and whether it can improve costs and efficiency of care.