Ground-level ozone (O3) and fine particulate matter (PM2.5) are associated with increased risk of mortality. We quantify the burden of modeled 2005 concentrations of O3 and PM2.5 on health in the United States. We use the photochemical Community Multiscale Air Quality (CMAQ) model in conjunction with ambient monitored data to create fused surfaces of summer season average 8-hour ozone and annual mean PM2.5 levels at a 12 km grid resolution across the continental United States. Employing spatially resolved demographic and concentration data, we assess the spatial and age distribution of air-pollution-related mortality and morbidity. For both PM2.5 and O3 we also estimate: the percentage of total deaths due to each pollutant; the reduction in life years and life expectancy; and the deaths avoided according to hypothetical air quality improvements. Using PM2.5 and O3 mortality risk coefficients drawn from the long-term American Cancer Society (ACS) cohort study and National Mortality and Morbidity Air Pollution Study (NMMAPS), respectively, we estimate 130,000 PM2.5-related deaths and 4,700 ozone-related deaths to result from 2005 air quality levels. Among populations aged 65–99, we estimate nearly 1.1 million life years lost from PM2.5 exposure and approximately 36,000 life years lost from ozone exposure. Among the 10 most populous counties, the percentage of deaths attributable to PM2.5 and ozone ranges from 3.5% in San Jose to 10% in Los Angeles. These results show that despite significant improvements in air quality in recent decades, recent levels of PM2.5 and ozone still pose a nontrivial risk to public health.