In patients with multiple sclerosis (MS), we investigated whether the extent of cerebral grey matter (GM) pathology is associated with the presence and severity of fatigue. We quantified cerebral GM pathology in 28 MS patients (14 with fatigue and 14 without fatigue) using magnetization transfer (MT) and diffusion tensor (DT) magnetic resonance imaging (MRI). The average MT ratio and mean diffusivity from cerebral GM did not differ between fatigued and non-fatigued patients. Fatigued and non-fatigued patients also did not differ in terms of GM pathology of the cerebral cortex of the frontal lobe and basal ganglia. No correlations were found between the fatigue severity scale scores and any of the MT- and DT-MRI quantities. These preliminary results suggest that structural GM pathology is not a major contributing factor to the development of fatigue in patients with MS.