Non-alcoholic fatty liver disease (NAFLD) is currently recognized as one of the leading causes of chronic liver disease related to the increased prevalence of obesity and metabolic syndrome. NAFLD is a common disorder, mostly benign and reversible, nevertheless a small proportion of patients will develop non-alcoholic steatohepatitis (NASH). NASH can progress to the whole spectrum of disease severity from advanced fibrosis to cirrhosis, hepatocellular carcinoma and the need for liver transplants. This study aimed to estimate the social costs and health losses associated to NAFLD in Portugal for 2017. A population-based multiple cohort model was designed to estimate the distribution of the prevalence of the different disease progression states based on cumulative disease incidence over time. Disease burden was measured in Disability-Adjusted Life Years (DALY), estimated as the sum of Years of Life Lost (YLL) due to premature mortality and Years Lost due to Disability (YLD). Costs to the healthcare system associated to NAFLD were also estimated using a prevalence approach. Incidence and prevalence of NAFLD in Portugal were retrieved from a population-based study. Adjusted prevalence of NAFLD was 17.0%, in 2017. During this year, there were 55 deaths attributed to NASH that resulted in the loss of 952 YLL. A total of 50 YLD were attributable to NASH. The total disease burden was 1,002 DALY. The estimated direct cost attributable to NAFLD progression in 2017 was approximately 61 million €. The total burden attributable to NAFLD is quite low, compared to other diseases such as heart failure or hypercholesterolemia. However, NAFLD is frequently associated with metabolic comorbidities including obesity, insulin resistance and type 2 diabetes, which makes people with NAFLD a high-risk group. Studies investigating NAFLD should include other comorbidities associated with complex and dynamic diseases to capture its full impact beyond liver diseases.