The COVID-19 pandemic has a close relationship with local environmental conditions. This study explores the effects of climate characteristics and air pollution on COVID-19 in Isfahan province, Iran. A number of COVID-19 positive cases, main air pollutants, air quality index (AQI), and climatic variables were received from March 1, 2020, to January 19, 2021. Moreover, CO, NO 2 , and O 3 tropospheric levels were collected using Sentinel-5P satellite data. The spatial distribution of variables was estimated by the ordinary Kriging and inverse weighted distance (IDW) models. A generalized linear model (GLM) was used to analyze the relationship between environmental variables and COVID-19. The seasonal trend of nitrogen dioxide (NO 2 ), wind speed, solar energy, and rainfall like COVID-19 was upward in spring and summer. The high and low temperatures increased from April to August. All variables had a spatial autocorrelation and clustered pattern except AQI. Furthermore, COVID-19 showed a significant association with month, climate, solar energy, and NO 2 . Suitable policy implications are recommended to be performed for improving people's healthcare and control of the COVID-19 pandemic. This study could survey the local spread of COVID-19, with consideration of the effect of environmental variables, and provides helpful information to health ministry decisions for mitigating harmful effects of environmental change. By means of the proposed approach, probably the COVID-19 spread can be recognized by knowing the regional climate in major cities. The present study also finds that COVID-19 may have an effect on climatic condition and air pollutants.