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Perfusion changes in white matter (WM) lesions and normal-appearing brain regions play an important pathophysiological role in multiple sclerosis (MS). However, most perfusion imaging methods require exogenous contrast agents, the repeated use of which is discouraged. Using resting-state functional MRI (rs-fMRI), we aimed to investigate differences in perfusion between white matter lesions and normal-appearing brain regions in MS and healthy participants. A total of 41 MS patients and 41 age- and sex-matched healthy participants received rs-fMRI, from which measures of cerebral hemodynamics and oxygenation were extracted and compared across brain regions and study groups using within- and between-group nonparametric tests, linear mixed models, and robust multiple linear regression. We found longer blood arrival times and lower blood volumes in lesions than in normal-appearing WM. Higher blood volumes were found in MS patients’ deep WM lesions compared to healthy participants, and blood arrival time was more delayed in MS patients’ deep WM lesions than in healthy participants. Delayed blood arrival time in the cortical grey matter was associated with greater cognitive impairment in MS patients. Perfusion imaging using rs-fMRI is useful for WM lesion characterization. rs-fMRI-based blood arrival times and volumes are associated with cognitive function.