According to the epidemiological surveys, ambient air pollution has directly related to mortality and different diseases such as cardiovascular and respiratory defects. Among the atmospheric contaminants, criteria air ones (NO2, O3, PM2.5/10, SO2) demonstrated that have particular importance in the community disease. The overall goal of this paper was to study the impact of criteria air contaminants on the health of the inhabitants of Shiraz city, Iran. To accomplish this, the AirQ2.2.3 software was applied. The results of the study revealed that the annual average NO2, SO2, PM2.5, PM10, and O3 concentrations are 39.98, 27.6, 14.35, 46.16, and 120.03 μg/m3 in 2016 and 30.27, 23.97, 16.45, 51.65, and 52.58 μg/m3 in 2017. The total International Classification of Diseases (ICD), cardiovascular, and respiratory mortalities caused by air contaminants in Shiraz was predicted as 911, 628, and 182 cases in 2016, and 346, 370, and 82 cases in 2017, respectively. Sulfur dioxide (SO2) had the greatest rate of total mortality with the attributable equivalent of 4.3% in 2016, but this value has been decreased to 0.42% in 2017. The findings of this research revealed that air contamination has caused problems in Shiraz city according to the predicted results. The findings of this work provide useful data for regional and national health policymakers, who should take decisions to develop strategies for control air contaminants and estimate the cost-effectiveness of interventions.