BACKGROUND: The incidence of Escherichia coli bloodstream infections (BSI) is high and increasing. We aimed to describe the effect of season and temperature on the incidence of E. coli BSI and antibiotic-resistant E. coli BSI and to determine differences by place of BSI onset. METHODS: All E. coli BSI in adult Israeli residents between January 1, 2018 and December 19, 2019 were included. We used the national database of mandatory BSI reports and outdoor temperature data. Monthly incidence and resistance were studied using multivariable negative binomial regressions with season (July-October vs. other) and temperature as covariates. RESULTS: We included 10,583 events, 9012 (85%) community onset (CO) and 1571 (15%) hospital onset (HO). For CO events, for each average monthly temperature increase of 5.5 °C, the monthly number of events increased by 6.2% (95% CI 1.6-11.1%, p = 0.008) and the monthly number of multidrug-resistant events increased by 4.9% (95% CI 0.3-9.7%, p = 0.04). The effect of season was not significant. For HO events, incidence of BSI and resistant BSI were not associated with temperature or season. CONCLUSION: Temperature increases the incidence of CO E. coli BSI and CO antibiotic-resistant E. coli BSI. Global warming threatens to increase the incidence of E. coli BSI.