Background There is strong evidence showing that sedentary behaviour time increase the risk to develop several chronic diseases and to premature death. The economic consequences of this risk have never been evaluated in France. The aim of this study was to estimate the economic burden of prolonged sedentary behaviour in France. Methods Based on individual sedentary behaviour time, relative risk to develop cardiovascular disease, colon cancer, breast cancer and all-causes of premature mortality were identified. From relative risk and prevalence of sedentary behaviour time, a population attributable fraction approach was used to estimate the yearly number of cases for each disease. Data from the National Health Insurance were used to calculate the annual average costs per case for each disease. Disease-specific and total healthcare costs attributable to prolonged sedentary behaviour time were calculated. Indirect costs from productivity loss due to morbidity and premature mortality were estimated using a friction cost approach. Results In France, 51 193 premature deaths/year appear related to a prolonged daily sedentary behaviour time. Each year prolonged sedentary behaviour cost 494 million € for the national health insurance. Yearly productivity loss due to premature mortality attributable to prolonged sedentary behaviour cost 507 million € and yearly productivity loss due to morbidity cost between 43 and 147 million €. Conclusion Significant saving and many deaths could be avoided by reducing prolonged sedentary behaviour prevalence in France. To address this issue, strong responses should be implemented to tackle sedentary behaviour, complementary to physical activity promotion.