While striatal and thalamic networks have been linked with fatigue in MS, they haven’t been explored in any young adult MS population. Further probing is needed to fully understand the fatigue correlate in MS and how it compares with differences between healthy controls and MS patients. In this study, we compared resting state functional connectivity measures in healthy controls, fatigued, and non-fatigued MS patients. Our results demonstrate that fatigue correlates with deficits in subcortical connectivity with several resting state networks. We found overlap between certain MS-related and fatigue-related changes, providing further insight into MS pathology and its fatigue correlate.