Objective: Severe fatigue is a prevalent and disabling symptom in Multiple Sclerosis (MS). This study tested if a fatigue and physical activity-related attentional bias (AB), and a somatic interpretation bias (IB) is present in severely fatigued patients with MS, compared to healthy controls and patients with chronic fatigue syndrome (CFS/ME). Method: Severely fatigued patients with MS or CFS/ME and healthy controls completed a Visual Probe Task (VPT) assessing fatigue and physical activity-related AB, and an IB task that assesses the tendency to interpret ambiguous information in either a somatically threatening way or in a more neutral manner. The VPT was completed by 38 MS patients, 44 CFS/ME patients, and 46 healthy controls, the IB task by respectively 156, 40 and 46 participants. Results: ANOVA showed no statistical significant group differences in a fatigue-related AB or physical activity-related AB (omnibus test of interaction between topic*condition: F2,125 = 1.87; p = .159). Both patient groups showed a tendency to interpret ambiguous information in a somatically threatening way compared to healthy controls (F1,2 = 27.61, p < .001). This IB was significantly stronger in MS patients compared to ME/CFS patients. IB was significantly correlated with cognitive responses to symptoms in MS patients. Conclusion: MS patients tend to interpret ambiguous information in a somatically threatening way. This may feed into unhelpful ways of dealing with symptoms, possibly contributing to perpetuation of severe fatigue in MS. Keywords: attentional bias, interpretation bias, fatigue, multiple sclerosis<br/
