Abstract Background: Multiple sclerosis (MS) is a chronic autoim-mune disease that affects the central nervous system. Microglia and macrophages have a substantial role in myelin and axonal degeneration by causing neuro-inflammatory damage. Soluble CD 163 one of the myeloid linage biomarkers, showed a better correlation with monocyte count in the CSF of MS patients. Aim of Study: In the current case control observational study, we aimed to assess serum level of sCD163 as an immunological non-invasive marker for MS activity. Patients and Methods: Sixty relapsing remitting multiple sclerosis (RRMS) patients were included and divided into 2 groups based on disease activity. Twenty-eight matched healthy controls were included and all subjects' serum levels of sCD163 were measured using ELISA. Results: This study demonstrated a highly significant-difference between the whole patients compared to controls with a concomitantno statistically significant difference between the patients' groups. Conclusion: This study emphasized the relevance of serum level of sCD 163 as a non-invasive immunological biomarker in the diagnostic panel of MS reflecting the inflammatory process rather than the activity status of the patients.