Background & purpose: Air pollution has been known as one of the most effective factors on cardiovascular, pulmonary and infectious diseases. This study aims to determine the relation between mortality rate and air pollution in Mashhad during 2007-2009. Materials & Methods: Data of air pollution, mortality rate and geographic factors were collected during 2007-2009 and analyzed. Mortality rate, the average PSI of individual pollutants , temperature and moisture were weekly measured and the diagrams were then drawn according to the methods of statistical correlation and regression analysis of air pollution and mortality rate. Results: According to the findings, there was no significant relation between CO and mortality rate, but the other pollutants played a significant role in this regard. The maximum correlation was obtained for SO2 and O3 in the concentrations of 0.936 and 0.154 ppm, respectively, but in the final model for all pollutants and weather variables, only PSI for O3, season and humidity showed significant change. Conclusion: O3 has increased during three years of research and has been the leading cause of death among the pollutants. Most deaths occurred in cold seasons. Among all pollutants, the maximum concentration of SO2 was in winter and the maximum concentration of O3 was in spring and summer 2009.