Patients with multiple sclerosis (MS) often show alexithymia, but brain mechanisms underlying this emotional disorder remains unknown. We used fMRI to investigate alterations of emotion processing and emotion regulation in patients with MS, and their relationships with alexithymia. Nineteen MS patients with minimal disability and twenty healthy control (HC) participants took part in this cross-sectional study. During fMRI, participants viewed scenes conveying negative or positive emotions, and were asked to rate the intensity of their emotional state 1) after spontaneous viewing and 2) after emotion regulation (cognitive reappraisal). Self-reported questionnaires targeting alexithymia but also other affective disorders were collected, in addition to functional and anatomical MRI. We compared brain activity and functional connectivity between each group during emotion processing and reappraisal. Moreover, we performed correlation analyses between affective questionnaire scores, subjective emotion ratings, brain activity, and structural integrity. Results showed a higher rate of alexithymia in MS patients. Globally, subjective ratings of emotional state were similar between MS and HC during both spontaneous perception and reappraisal. However, in both task conditions, the MS group showed increased responses to emotional scenes in the orbital IFG, relative to controls. Moreover, during the reappraisal of negative scenes, these regions displayed increased functional connectivity with the amygdala, whose activity was positively correlated with alexithymia severity in MS. Our findings suggest a direct relationship between alexithymia and a lack of down-regulation of amygdala activity in response to negative emotions during reappraisal in MS. Moreover, they highlight compensatory mechanisms in minimally disabled MS patients, recruiting fronto-striatal circuits, which may serve to preserve homeostasis of amygdala activity and affective state.