Copper is an essential microelement for animals, and not only it has been used as a feed additive at pharmacological doses in swine production to improve growth performance, but it also has an effect on intestinal microbes by enhancing host bacterial resistance. However, there are few reports on the effects of pharmacological doses of copper on intestinal microorganisms and the antimicrobial resistance profiles of pathogenic bacteria, such as Escherichia coli, in pigs. Therefore, this study aimed to investigate the effects of pharmacological doses of copper on the microbial communities in the hindgut and the antimicrobial resistance profiles of E. coli in weaned piglets. Twenty-four healthy weaned piglets aged 21 ± 1 days and with an average weight of 7.27 ± 0.46 kg were randomly divided into four groups. The control group was fed a basal diet, while the treatment groups were fed a basal diet supplemented with 20, 100, or 200 mg copper/kg feed, in the form of CuSO 4. Anal swabs were collected at 0, 21, and 42 days of the trial, and E. coli was isolated. Meanwhile, the contents of the ileum and cecum from the control and 200 mg copper/kg feed groups were collected at 21 and 42 days for microbial community analysis and E. coli isolation. All isolated E. coli strains were used for antimicrobial resistance profile analysis. A pharmacological dose of copper did not significantly change the diversity, but significantly affected the composition, of microbial communities in the ileum and cecum. Moreover, it affected the microbial metabolic functions of energy metabolism, protein metabolism, and amino acid biosynthesis. Specifically, copper treatment increased the richness of E. coli in the hindgut and the rates of E. coli resistance to chloramphenicol and ciprofloxacin. Moreover, the rate of E. coli resistance to multiple drugs increased in the ileum of pigs