Background: Multiple sclerosis (MS) is the most common debilitating chronic autoimmune and inflammatory disorder of the central nervous system. Compared to the general population, MS patients are at a higher risk of contracting various diseases. Objectives: This study aimed to determine the challenges related to the injection of COVID-19 vaccines in people with MS. Methods: In this qualitative research that was conducted on patients with MS, the data were collected in a secure environment through semi-structured interviews. We continued the interviews until data saturation, which was reached after 10 interviews, but 2 more interviews were conducted to make sure of data saturation. The duration of each interview was 30 - 45 minutes, depending on each patient's condition. The data were managed in MAXQDA 10. Results: Of the participants, 66% were female, and the average age of the patients was 47 years. After analyzing the interviews, 4 main categories and 19 subcategories were extracted: mental concerns (hearing rumors, hearing news of death due to COVID-19, worrying about the unknowns of new vaccines, and worrying about side effects and treatment interactions), quarantine suffering (movement complications, depression, weak immune system, social distancing, and compliance with health protocols), educational resources (doctors, clinic staff, national media, cyberspace, and family) and personal experiences (effectiveness of the COVID-19 vaccine, reduction of symptoms compared to unvaccinated people, and having no complications). Conclusions: It is essential to take measures to decrease the existing challenges. For example, the patients were afraid of drug interactions and the lack of full understanding of the disease by doctors. In general, they had many questions, while they did not know a reliable source of information. They chose doctors as the most reliable source; this choice shows the importance and capacity of the doctor's position in relation to vaccination, which can be used to explain and promote vaccination in schools, offices, factories, and other parts of society. Besides, in relation to research on new diseases, a task force should be formed for each disease, and the mutual impacts of diseases and their drug interactions should be investigated; in this way, fewer concerns and problems arise during vaccination and treatment.