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Purpose: The association between air pollutant (PM 2.5 , PM 10 , NO 2 , and O 3 ) concentrations and daily number of COVID-19 confirmed cases and related deaths were evaluated in three major Iranian cities (Tehran, Mashhad, and Tabriz)., Methods: Hourly concentrations of air pollutants and daily number of PCR-confirmed cases and deaths of COVID-19 were acquired (February 20 th , 2020 to January 4 th , 2021). A generalized additive model (GAM) assuming a quasi-Poisson distribution was used to model the associations in each city up to lag-day 7 (for mortality) and 14 (for morbidity). Then, the city-specific estimates were meta-analyzed using a fixed effect model to obtain the overall relative risks (RRs)., Results: A total of 114,964 confirmed cases and 21,549 deaths were recorded in these cities. For confirmed cases, exposure to PM 2.5 , NO 2 , and O 3 for several lag-days showed significant associations. In case of mortality, meta-analysis estimated that the RRs for PM 2.5 , PM 10 , NO 2 , and O 3 concentrations were 1.06 (95% CI: 0.99, 1.13), 1.06 (95% CI: 0.93, 1.19), 1.15 (95% CI: 0.93, 1.38), and 1.07 (95% CI: 0.84, 1.31), respectively. Despite several positive associations with all air pollutants over multiple lag-days, COVID-19 mortality was only significantly associated with NO 2 on lag-days 0-1 and 1 with the RRs of 1.35 (95% CI: 1.04, 1.67) and 1.16 (95% CI: 1.02, 1.31), respectively., Conclusion: This study showed that air pollution can be a factor exacerbating COVID-19 infection and clinical outcomes. Actions should be taken to reduce the exposure of the public and particularly patients to ambient air pollutants., Supplementary Information: The online version contains supplementary material available at 10.1007/s40201-021-00736-4., Competing Interests: Conflicts of interest/Competing interestsThe authors declare no conflict of interests., (© Springer Nature Switzerland AG 2021.)