Objectives: This study aims to estimate direct and indirect health economic costs associated with government and out-of-pocket (OOP) expenditure based on health care service utilization and lost income of participants and carers, as reported by Australian Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patient survey participants.

Design: A cost of illness study was conducted to estimate Australian cost data for individuals with a ME/CFS diagnosis as determined by the Canadian Consensus Criteria (CCC), International Consensus Criteria (ICC), and the 1994 CDC Criteria (Fukuda).

Setting and participants: Survey participants identified from a research registry database provided self-report of expenditure associated with ME/CFS related healthcare across a 1-month timeframe between 2017 and 2019.

Main outcome measures: ME/CFS related direct annual government health care costs, OOP health expenditure costs, indirect costs associated with lost income and health care service use patterns.

Results: The mean annual cost of health care related expenditure and associated income loss among survey participants meeting diagnostic criteria for ME/CFS was estimated at $14.5 billion. For direct OOP and Government health care expenditure, high average costs were related to medical practitioner attendance, diagnostics, natural medicines, and device expenditure, with an average attendance of 10.6 referred attendances per annum and 12.1 GP visits per annum related specifically to managing ME/CFS.

Conclusions: The economic impacts of ME/CFS in Australia are significant. Improved understanding of the illness pathology, diagnosis, and management, may reduce costs, improve patient prognosis and decrease the burden of ME/CFS in Australia.