BACKGROUND: Considering the potential COVID-19 impact on pwMS health and the importance of vaccination for this population, we decided to assess: (a) pwMS' beliefs and knowledge on COVID-19 pandemic; (b) their acceptance towards COVID-19 vaccination and (c) pwMS' opinions on general vaccination. METHODS: Observational study, based on a cross-sectional (10-20(th) September 2020) online survey, conducted in a cohort of pwMS' followed at two Portuguese hospitals. The survey included measures to characterize the sample and a questionnaire designed to assess the topics defined for this study. RESULTS: 270 respondents completed the full survey (response rate 58.2%). pwMS greatest concern during the pandemic was an aggravation of MS, especially by patients older than 50 years old. Almost 40% of the patients older than 50 felt that the pandemic negatively affected their MS related medical assistance. Most patients believed they would recover from COVID-19 infection. More than half of the responders feared a MS aggravation if they got COVID-19; this was more pronounced in patients with progressive MS. About 12% of the participants did not want to be vaccinated and almost 40% was unsure. Regarding vaccines in general, almost a third of the participants feared their side effects or MS related complications. CONCLUSION: Having knowledge of pwMS' opinions on COVID-19 pandemic impact and vaccination is useful to better address these issues. Fears and expectations towards vaccination must be discussed with pwMS.