Background/Objective We aimed to investigate whether cervical cord damage and dysfunction is associated with the presence and severity of fatigue in multiple sclerosis (MS) using a multiparametric magnetic resonance (MR) approach. Methods: Cervical cord functional magnetic resonance imaging (fMRI) during a tactile stimulation of the right hand, and structural brain and cord MRI were acquired from 20 controls, 15 MS patients without fatigue (NF) and 20 MS patients with fatigue (F). Between-group differences in the extent of focal lesions and diffusivity abnormalities in the brain and cord, cord-normalized cross-sectional area (CSAn) and fMRI activity were assessed. Results: All structural MRI measures differed significantly among groups, except for cord lesion number and CSAn. Compared with controls, NF-MS patients experienced higher cord recruitment ( p=0.04). Compared with F-MS, NF-MS patients had a lower brain normal-appearing white matter average fractional anisotropy ( p=0.001) and increased cord recruitment ( p=0.02). In patients with MS, the extent of cord recruitment was correlated with the severity of fatigue ( r=-0.34, p=0.04). Compared with the other two groups, F-MS patients had a more diffuse recruitment of cord quadrants on the axial and longitudinal planes. Conclusions: Abnormalities of function, but not of structure, of the cervical cord are likely to contribute to the pathogenesis of fatigue in MS.