Objective: Functional magnetic resonance imaging (fMRI) studies conducted on patients with multiple sclerosis (MS) indicated that execution of motor tasks determines an increased recruitment of some areas of the fronto-parietal circuit associated with grasping and manipulating objects. In addition, neuroimaging research on healthy humans disclosed that a number of fronto-parietal areas involved in hand action execution are also activated during hand action observation. We used fMRI to compare patterns of haemodynamic activity evoked by observation of grasping actions in early relapsing remitting MS (RRMS) patients and in normal controls. Methods: 12 right-handed early RRMS patients have been recruited. Further, 15 sex- and age-matched right-handed healthy volunteers served as controls. Using a 1.5T scanner, functional images were obtained with a single shot echo-planar T2*-weighted sequence in order to measure blood oxygenation level-dependent contrast throughout the whole brain (32 axial slices, slice thickness 3.5 mm/0.5 mm gap, matrix 64 x 64 voxels, FOV = 224 x 224 mm2, flip angle = 90°, TR = 3 s, TE = 50 ms). During scanning participants were requested to observe static images depicting a human hand either grasping an object (grasping condition) and resting alongside an object (control condition). Experimental conditions were presented in a block design with blocks' duration of 15 s. Functional volumes were pre-processed and analysed using the software SPM5 by realignment and by normalization to the standard space defined by the Montreal Neurological Institute (MNI) template. Lastly, volumes were smoothed using an 8 mm isotropic Gaussian kernel. High-pass filtering was also applied. Results: Ours results suggest that, among other areas, action observation (grasping condition) evoked an increased activation of both the precentral gyrus, bilaterally and the inferior occipital gyrus, billaterally in MS patients as compared to controls. During the control condition (human hand resting alongside an object), compared to healthy volunteers, patients with MS had more significant activations of the left inferior occipital gyrus. The level for these contrasts was set at p<0.001 (uncorrected; extent threshold of at least 10 contiguous voxels). Conclusions: These findings suggest that during hand action observation early RRMS patients show an increased activation in regions of the premotor cortex known to be involved in action observation. This may indicate that the "over-activation mechanism" emerged in RRMS patients during action execution tasks may extend to action understanding situations.