Abstract To assess mortality risks and burdens associated with short-term exposure to wildfire-related fine particulate matter with diameter ≤ 2.5 μm (PM 2.5 ), we collect daily mortality data from 2000 to 2016 for 510 immediate regions in Brazil, the most wildfire-prone area. We integrate data from multiple sources with a chemical transport model at the global scale to isolate daily concentrations of wildfire-related PM 2.5 at a 0.25 × 0.25 resolution. With a two-stage time-series approach, we estimate (i) an increase of 3.1% (95% confidence interval CI: 2.4, 3.9%) in all-cause mortality, 2.6% (95%CI: 1.5, 3.8%) in cardiovascular mortality, and 7.7% (95%CI: 5.9, 9.5) in respiratory mortality over 0–14 days with each 10 μg/m 3 increase in daily wildfire-related PM 2.5 ; (ii) 0.65% of all-cause, 0.56% of cardiovascular, and 1.60% of respiratory mortality attributable to acute exposure to wildfire-related PM 2.5 , corresponding to 121,351 all-cause deaths, 29,510 cardiovascular deaths, and 31,287 respiratory deaths during the study period. In this study, we find stronger associations in females and adults aged ≥ 60 years, and geographic difference in the mortality risks and burdens.