OBJECTIVES: To identify drivers of overall cost associated with the current management of Dravet syndrome (DS), and compare costs for high and low severity patients in the EU5 (France, Germany, Italy, Spain and UK). METHODS: The 2016 DISCUSS survey included 344 paediatric and adult patients, and their caregivers, residing in the EU5. Health and social care resource use and productivity were summarised. Direct healthcare costs were calculated using participant- and literature-reported health service costs, as appropriate. Current seizure burden was quantified (using composite seizure frequency scores) and healthcare costs for patients with high and low seizure burden compared. RESULTS: The annual direct cost per DS patient in the EU5 was $15,885 ($9,783 excluding anti-epileptic drugs [AEDs]), comprising $7,957 for seizure-related ($1,854 excluding AEDs) and $7,929 for non-seizure-related symptoms. Drivers of total direct cost are AEDs (38%) and non-seizure-related therapies (50%). Excluding AEDs, non-seizure-related costs contribute 81% of direct costs. Physiotherapy and speech therapy account for the bulk (79%) of non-seizure-related costs. In the highest seizure frequency subgroup, annual per-patient seizure-related healthcare and physiotherapy costs were significantly higher than in the lowest subgroup (emergency admissions, $863 vs $391; ambulance calls $1,140 vs $389; epilepsy specialists $824 vs $337; physiotherapy $1,963 vs $894). Financial support varied across countries, with families paying out of their own pocket facing high costs. Most caregivers (83%) reported an influence on their career choices, over a quarter (27%) were unemployed, and 31% of those in work had missed two or more working days in the past four weeks for their child’s emergency or routine needs. CONCLUSIONS: This is the first study to estimate the cost of managing DS in a large European cohort. Non-seizure-related symptoms in DS contribute to approximately half of all healthcare costs and a high seizure burden is associated with higher healthcare costs.