Introduction: The Danish national health registers were used to investigate the economic burden of obesity, associated costs of comorbidities and a breakdown into direct and indirect costs. Methods: The study population comprised all Danish adult citizens registered with a hospital diagnosis of obesity in the Danish National Patient Register between 2002 and 2018. Cases were matched with five controls via the Danish Civil Registration System. We estimated the difference in total healthcare costs and indirect costs between cases and controls and the difference in healthcare resource utilization. In a sub-analysis, we estimated total healthcare costs for persons who had been registered with one or more of 11 predefined comorbidities. Results: People with obesity experienced a statistically significant twofold increase in average direct healthcare costs per year (EUR 5,934), compared with controls (EUR 2,788) and had statistically significantly higher indirect costs compared to controls. Total healthcare costs for people with obesity and one or more of the 11 comorbidities were 91.7%–342.8% higher than total healthcare costs of the population with obesity but none of the 11 comorbidities. Conclusion: Obesity was associated with an increase in both direct and indirect costs. The presence of comorbidities was associated with additional healthcare costs. Key points: Obesity is associated with an increase in direct and indirect costs in Denmark. Comorbidities are associated with additional healthcare costs.