OBJECTIVES: Multiple sclerosis (MS) is a prevalent, chronic and disabling disease, mainly affecting young adults. The aim of the present work is to analyse the cost of the informal care of MS according to disability, in different Spanish regions. METHODS: Patients with clinical diagnosis of MS, from different Spanish regions, were selected between december 2006 and december 2010. The patients were divided in 3 groups based on their disability: mild (EDSS 0-3,5), moderate (EDSS 4,0-6,5) and severe (7,0-9,5).  They were invited to answer a questionnaire, with demographic, social, employment status data, clinical aspects, as well as data about the consumption of sanitary and no-sanitary resources during the MS process. The replacement method was used to estimate informal costs. RESULTS: We analized 1107 pacients and 317 caregivers. The percentage of patients requiering informal care increased with disability, ranging from 7% (mild disability) to 73% (severe disability) and daily hours of informal care per patient, 0.4 (mild disability) to 11.8 (severe disability). These informal cares can also vary depending on the Spanish region analyzed. The caregiver mean age was 53 years, is mostly the patient's partner (54%) and has been practicing as a caregiver a mean of 10 years. The estimated cost of informal care increased with disability, ranging from 777 euros/ patient/year (mild disability) to 26.987 euros/patient/year (severe disability). The cost grew to 45% of the total cost of the disease in advanced stages. CONCLUSIONS: The estimated cost of informal care increased with disability, ranging from 777 euros/ patient/year (mild disability) to 26,987 euros/patient/year (severe disability). It represented almost half of the total cost of the disease in advanced stages.