OBJECTIVES: Multiple sclerosis (MS) is a debilitating condition that primarily affects young adults. The recent development of more effective yet costly drugs aimed at delaying the progression of the disease further adds to the necessity of evaluating the costs associated with MS from the societal perspective and the disease burden. We aimed to estimate the disease and economic burden of MS from the societal perspective in Colombia during 2020. METHODS: The disease burden was estimated following the methodology proposed by Global Burden of Disease Study 2019. Regarding the economic burden, an average cost per patient was estimated and applied to national MS cases. Specifically, the average direct medical costs per patient were obtained from an insurance company's database and validated by 2 clinical experts. Nonmedical direct and indirect costs were estimated based on the data collected from a sample of MS patients. RESULTS: Colombia lost an estimated 3455 disability-adjusted life years because of MS in 2020. The disease burden was mainly attributed to deaths (65.5%, 2264 years of life lost). Disability-adjusted life years were 1.7 times higher in women than in men. Risaralda was the municipality with the highest population-adjusted MS disease burden, followed by Bogotá, DC. The associated cost of MS was USD 8.2 million, of which 88% was attributed to direct medical costs. CONCLUSIONS: MS is a high-cost disease in Colombia with an increasing prevalence. The results presented in this study will help determine the allocation of resources when planning health care services.