The prevalence of overweight and obesity has increased in the last decades, posing significant health and economic impacts globally. These conditions are related to several non-communicable diseases, including cardiovascular disease, type II diabetes and cancer. This study estimated the disease burden and healthcare costs associated with overweight and obesity in the adult population in mainland Portugal, in 2018. Burden of disease was measured in disability-adjusted life years (DALY) following Global Burden of Disease (GBD) methodology. DALY were calculated as the sum of years of life lost (YLL) and years lived with disability (YLD). The analyses included morbidity, mortality and related costs directly related to overweight and obesity, as well as the attributable morbidity, mortality and related costs of of 25 selected diseases related to obesity (DrO). A prevalence-based cost analysis was conducted a from the perspective of the public National Health Service, including costs related to inpatient, outpatient care and pharmacological treatment. In 2018, total DALY amounted to 260,943, with 75% due to premature death (196,438 YLL) and 25% due to disability (64,505 YLD). The economic burden of overweight and obesity was estimated at approximately € 1,148 million. Of these, approximately € 13.3 million (1%) were costs related to the treatment of obesity, and the remaining were costs of DrO attributed to overweight and obesity. Outpatient care corresponded to 43% of total costs, pharmacological treatment 38%, and inpatient care 19%. Cardiovascular and cerebrovascular diseases were the largest contributor to total costs (38%), followed by type II diabetes (34%). Overweight and obesity incur a large disease and economic burden to the public healthcare sector, representing approximately 0.6% of the country´s gross domestic product and 5.8% of public health expenditures.