Background: Although many types of immune cells are involved in multiple sclerosis (MS) progression, activated monocytes are believed to be one of the first to arrive at the brain and initiate inflammation. However, little is known about how the different monocyte subsets (classical, intermediate and non-classical) are involved in MS. Ain of the work: The current study aims to investigate the presence of different subsets of monocytes in relapsing-remitting MS (RRMS) Egyptian patients and their correlation with disease activity. Patients and Methods: This study included 44 RRMS patients (22 patients in relapse, 22 patients in remission), diagnosed according to the 2017 MacDonalds criteria, and 44 age-and sex-matched healthy controls. Full personal and medical histories were taken from the patients and Expanded Disability Status Scale (EDSS) was done to assess patients' disability. Characterization of monocyte subsets was done by flowcytometry for all participants. Results: The percentage of classical, intermediate, and non-classical monocyte subsets showed a statistically significant increase in MS patients than controls with p values (0.029, 0.049, 0.043) respectively. No statistically significant difference in the frequency of the classical and intermediate monocyte subsets with any of the clinical parameters. However, patients with evidence of activity in MRI have a significantly high frequency of non-classical monocytes with p value (0.002). No statistically significant difference in the frequency of the non-classical monocyte subset with the other clinical parameters. Conclusion: In MS relapse and remission, the three monocyte subsets (classical, intermediate & non-classical) increase significantly. This increase denotes the vital role of monocytes in disease pathology, as they might be related to disease activity, especially the non-classical monocyte subset. This finding makes monocytes a promising therapeutic target and a possible diagnostic tool for MS.