Pathological data showed focal inflammation and regions of diffuse neuronal loss in the cortex of people with multiple sclerosis (MS). In this work, we applied a novel model ("soma and neurite density imaging (SANDI)") to multishell diffusion-weighted MRI data acquired in healthy subjects and people with multiple sclerosis (pwMS), in order to investigate inflammation and degeneration-related changes in the cortical tissue of pwMS. We aimed to (i) establish whether SANDI is applicable in vivo clinical data; (ii) investigate inflammatory and degenerative changes using SANDI soma fraction (f)-a marker of cellularity-in both cortical lesions and in the normal-appearing-cortex and (iii) correlate SANDI f with clinical and biological measures in pwMS. We applied a simplified version of SANDI to a clinical scanners. We then provided evidence that pwMS exhibited an overall decrease in cortical SANDI f compared to healthy subjects, suggesting global degenerative processes compatible with neuronal loss. On the other hand, we have found that progressive pwMS showed a higher SANDI f in the outer part of the cortex compared to relapsing-remitting pwMS, possibly supporting current pathological knowledge of increased innate inflammatory cells in these regions. A similar finding was obtained in subpial lesions in relapsing-remitting patients, reflecting existing pathological data in these lesion types. A significant correlation was found between SANDI f and serum neurofilament light chain-a biomarker of inflammatory axonal damage-suggesting a relationship between SANDI soma fraction and inflammatory processes in pwMS again. Overall, our data show that SANDI f is a promising biomarker to monitor changes in cellularity compatible with neurodegeneration and neuroinflammation in the cortex of MS patients.