We estimated mortality and economic loss attributable to PM2·5 air pollution exposure in 429 counties of Iran in 2018. Ambient PM2.5-related deaths were estimated using the Global Exposure Mortality Model (GEMM). According to the ground-monitored and satellite-based PM2.5 data, the annual mean population-weighted PM2·5 concentrations for Iran were 30.1 and 38.6 μg m-3, respectively. We estimated that long-term exposure to ambient PM2.5 contributed to 49,303 (95% confidence interval (CI) 40,914-57,379) deaths in adults ≥ 25 yr. from all-natural causes based on ground monitored data and 58,873 (95% CI 49,024-68,287) deaths using satellite-based models for PM2.5. The crude death rate and the age-standardized death rate per 100,000 population for age group ≥ 25 year due to ground-monitored PM2.5 data versus satellite-based exposure estimates was 97 (95% CI 81-113) versus 116 (95% CI 97-135) and 125 (95% CI 104-145) versus 149 (95% CI 124-173), respectively. For ground-monitored and satellite-based PM2.5 data, the economic loss attributable to ambient PM2.5-total mortality was approximately 10,713 (95% CI 8890-12,467) and 12,792.1 (95% CI 10,652.0-14,837.6) million USD, equivalent to nearly 3.7% (95% CI 3.06-4.29) and 4.3% (95% CI 3.6-4.5.0) of the total gross domestic product in Iran in 2018.