question: BACKGROUND: The coronavirus outbreak, which emerged in Wuhan, China, in late 2019 and spread to the world, has changed each of our lives. OBJECTIVE: To investigate the effects of quarantine on depression, anxiety, sleep quality, fatigue, and SF-36 of multiple sclerosis (MS) patients during the COVID-19 outbreak and differences between healthy controls (HC). METHODS: Eighty-six MS patients and 65 HC patients were included in the study. Participants filled out the various scales through face-to-face interviews for mental health assessment from January 15 to February 15, 2021. RESULTS: When both groups were compared in terms of BECK-D inventory (p < 0.001), BECK-A inventory (p = 0.010), and FS (p < 0.001), the patient group had significantly higher results. Physical functioning (p < 0.001), physical role limitation (p = 0.001), energy vitality rates (p = 0.010), and general health perception (p < 0.001) were higher in the HC group. When MS patients were divided according to EDSS scores, BECK-A (p < 0.001), BECK-D (p = 0.001), and PSQI (p = 0.006) scores of the patients with EDSS > 3 were higher, while emotional role restriction rates (p = 0.006), energy and vitality (p = 0.018), and pain (p = 0.005) were significantly lower than those with EDSS ≤ 3. When MS patients were divided into two groups as who had COVID-19 and who did not and compared SF-36 subscale scores, pain, (p = 0.049) and mental status (p = 0.030) were obtained significant differences in the two groups. CONCLUSIONS: Our study revealed that MS patients, who are more susceptible to the new 'normal' that emerged during the pandemic period, are among the priority groups that should be supported in terms of mental health as well as physical health.