Low physical activity is a risk factor for the increasing burden of morbidity and mortality from non-communicable diseases, which is a significant problem in Thailand and globally. This study aimed to estimate the health burden associated with low physical activity in Thai adults in 2019, using a comparative risk assessment (CRA) framework. The estimation of the proportion of major non-communicable diseases attributable to low physical activity included breast cancer, colon cancer, type 2 diabetes, ischemic heart disease, and ischemic stroke in the entire population. Data on the prevalence of physical activity from the 6th national health examination survey, relative risk was taken from the global burden disease (GBD) in 2019, and mortality, (years of life lost; YLLs), (years lost due to disability; YLDs), and (disability-adjusted life years DALYs) in 2019 was derived from the Thailand BOD study. The study findings revealed that the majority of the Thai population aged 25-59 had high levels of physical activity, both among males and females, with slightly higher activity levels in males compared to females. However, over half of the elderly population aged 80 and above had low levels of physical activity. Additionally, it was found that patients with diabetes had the highest proportion of deaths due to low physical activity, accounting for 16.7% and 19.9% of all deaths from diabetes in males and females, respectively. This was followed by ischemic heart disease and ischemic stroke. Furthermore, low physical activity was identified as the cause of a substantial loss of disability-adjusted life years; DALYs, amounting to 298,630 DALYs (158,971 DALYs in males and 139,659 DALYs in females). The highest loss was attributed to ischemic heart disease, accounting for 44.3% of the total loss of DALYs due to low physical activity, followed by type 2 diabetes and ischemic stroke, respectively.