OBJECTIVE: To estimate the costs of multiple sclerosis (MS) in Poland according to severity of disease. METHODS: Enrolled were 148 outpatients with MS at 3 centres across Poland. Socio-demographic, clinical and resource utilization data were collected using a validated questionnaire over a 5-month period. Total, direct and indirect costs were compared among three groups categorised by disease severity (EDSS score): stages I, II and III, corresponding to mild (EDSS 1-3,5, n = 57), moderate (EDSS 4-6, n = 56) and severe (EDSS 6,5-8, n = 35) MS, respectively. Cost evaluation was performed from both the public payer and societal perspective. Due to absence of available opportunity costs, tariffs were used as an approximation. Human capital approach was used for calculation of indirect costs. Simple sensitivity analysis was performed by varying the tariffs, valuing caregiving at 40% of the average wage and taking into account extreme values of direct and indirect costs in each group. RESULTS: From the societal perspective the mean total cost /patient/d was estimated at 71,109 and 132 PLN for stage I, II and III respectively (1 PLN = €4). Regardless of EDSS stage indirect costs exceeded direct costs and were estimated at 46, 73, and 84 PLN/patient/d for stage I, II and III respectively. The increase of total, direct medical and indirect costs associated with progression of disease was statistically significant. The major medical cost drivers were rehabilitation and hospitalizations. The percentage of direct costs covered by public payer was 80% for stage I and II and 60% for stage III. Results were sensitive to the variation applied, but the overall trend remained as in the primary analysis. CONCLUSION: This study confirms that MS represents a high economic burden, with indirect costs greatly exceeding direct costs. As costs increase with disease progression, treatment efforts should focus on patients in the early stages of MS.