Multiple sclerosis (MS) is the most common inflammatory neurologic disease in young adults. Its pathological mechanisms include demyelination, neurodegeneration, and synaptopathy. Cognitive deficits occur in up to 65% of individuals with MS and affect both nonsocial (eg, information processing speed, memory, and executive functions) and social (ie, emotion recognition, theory of mind, and empathy) cognitive domains. In the last 3 decades, there has been a growing interest in social cognition and its relationship with neuropsychological, sociodemographic, and disease characteristics in individuals with MS. Uncovering the neuropathological correlates of social cognitive deficits is now a crucial aim that would also help us better understand the underlying mechanisms of social cognition. We reviewed 11 neuroimaging studies to investigate social cognition in MS. These studies focused mainly on facial emotion recognition and theory of mind, with the findings suggesting that a disrupted cortico-subcortical network forms the basis of social deficits involving both domains. We then interpreted these results in the context of multiple disconnection syndrome, which occurs as a result of axonal demyelination and degeneration within the connexome of several neural hubs devoted to social cognition. Heterogeneity in social cognitive performance, observed among our study participants, is discussed with reference to the cognitive reserve and brain reserve hypotheses. These reserves may explain why individuals with comparable clinical characteristics of MS may exhibit different cognitive profiles. Further research is required to generalize these findings to the MS population and to inform the development of effective interventions to improve psychosocial functioning in individuals with MS.