PROPOSE: Among antibiotic resistance cases, resistance to ß-lactam antibiotics is a major concern for the treatment of microbial infections. Furthermore, the prevalence of extended-spectrum ß-lactamases (ESBL) Escherichia coli (E. coli) in environment, food, and human resources of Iran has increased over the past few years. This study aimed to predict the relationship between the prevalence of ESBL E. coli in the environment and the food chains with the presence of this infection in people suspected of septicemia using fuzzy set qualitative comparative analysis model. METHODS: In this analytical cross sectional study samples were collected from the environment (hospital sewage, downstream and upstream urban sewage, and slaughterhouse sewage), food (chicken), and human chains (people suspected of septicemia) in Tehran province, Iran. This study was conducted from September to February 2019 and the prevalence of ESBL E. coli was calculated in each resource. Then, the relationship between the prevalence of ESBL E. coli in the environment and food chains and its prevalence in the human chain was predicted using the fuzzy set qualitative comparative analysis. RESULTS: The results showed the prevalence of ESBL E. coli in those suspected of septicemia in September, October, November, December, January and February was 58.1%, 60%, 33.3%, 100%, 43%, and 57.8%, respectively. Also, the results of the fuzzy set qualitative comparative analysis indicated hospital wastewater and chicken contamination with ESBL E. coli were the main causes of contamination with ESBL E. coli in people suspected of septicemia. CONCLUSIONS: According to the results of this study, if there is a contamination of hospital wastewater and chickens in an area, it can be claimed that people suspected of septicemia are infected with ESBL E. coli, and the percentage of this contamination can be high. On the other hand, controlling ESBL E. coli in hospital wastewater (environmental chain) and chickens (food chain) can prevent contamination in people with suspected septicemia.