Background: People with Multiple Sclerosis (MS) may be disproportionally impacted by COVID-19 as various factors important to their functioning and quality of life (QoL) are at-risk and/or compromised during the pandemic. In particular, the social distancing and quarantine practice during the pandemic may be detrimental for MS patients. Compared with the general population, MS patients may be under increased social strain and suffer worse health consequences from social isolation. To date, there has been no research examining the social consequences of pandemic on MS patients emotional and social health, and thus, our study aims to show this. Objectives: 1. Our primary objective is to investigate changes in mental health and social participation during the COVID-19 pandemic in people with MS. We hypothesize that anxiety, depression, and social participation have worsened during the COVID-19 pandemic. 2. Our secondary objectives are to identify the consequences of social isolation on mental health. We hypothesize that social isolation is associated with worse anxiety and depression since the COVID-19 pandemic. 3. Our tertiary objective is to identify the changes in mental health and social participation among MS patients who utilized in-person during the COVID-19 pandemic. We hypothesize that MS patients who utilized in-person visits experienced no significant changes in depression, anxiety, and social participation during the COVID-19 pandemic. Methods: This is a retrospective longitudinal study. 266 adults with MS followed at the Mellen Center at the Cleveland Clinic completed monthly surveys including demographic characteristics, MS classifications, depression, anxiety, and social health variables (social participation, satisfaction with social roles, social isolation). Results: Students T-Tests shows worse anxiety (95% CI [-5.03, – 3.05]; p-value < 0.001), worse depression (95% CI [-2.67, – 1.03]; p-value < 0.001), and worse satisfaction with social roles (95% CI [2.37, 3.95]; p-value < 0.001) since the COVID-19 outbreak (March 2020). Social isolation is associated with worse anxiety (95% CI [-8.98, – 4.58]; p-value < 0.001) and depression (95% CI [-6.88, – 3.24]; p-value < 0.001). However, individuals who had in-person visits before and after the outbreak didnt experience any changes in anxiety, depression, or social health. Conclusions: MS patients anxiety, depression, and social participation worsened during the COVID-19 pandemic. Social isolation is found to be associated with worse anxiety and depression. However, those who attended in-person visits for their MS treatment did not experience negative changes in their emotional or social health. These findings show that healthcare providers need to be alert to MS patients social health and the interplay between social and emotional health during the COVID-19 pandemic.