Air pollution is an important health risk concern and an economic burden, notably on low and middle-income countries. The aim of this study was to determine the mortality burden of cardiovascular and respiratory diseases, considering the relative risk due to air pollution and the economic valuation derived from life-years lost within the population of São Paulo, Brazil. This study was conducted considering a retrospective Health Impact Assessment (HIA) approach by means of daily time series of cardiovascular and respiratory deaths considering the population of São Paulo, Brazil from 2000 to 2011. Effects of particulate matter smaller than 10 μm (PM10) were estimated in Poisson generalized additive models. Single-day lag effects of air pollutant exposure were estimated for lags 0 through 3 day lags. Therefore, we obtained the Years of Life Lost (YLL) from Disability-Adjusted Life Years (DALY) method to estimate the burden of disease due to air pollution in São Paulo. Value of Life Year (VOLY) converted YLL component to economic losses. The results showed an association between PM10 and cardiovascular and respiratory mortality, lagged 3 days. Total years of life lost sums 231,691.8 years, meaning an economic loss of more than US$14.1 billion for all period. In conclusion, the knowledge regarding the costs of premature deaths related to air pollution could be useful to strengthen the government’s public policies and to facilitate decision making in the context of scarce resources.