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Simple Summary: The scientific community has recently turned its interest to wildlife, including birds, as a potential marker of environmental antimicrobial resistance. The aim of this work was to investigate the antimicrobial susceptibility of 100 commensal Escherichia coli strains isolated from wild birds admitted to the Veterinary Teaching Hospital of Perugia (Central Italy) and the possible presence of extended-spectrum beta-lactamase (ESBL)-producing E. coli and Salmonella spp. Antimicrobials have been selected on the basis of their relevance for public health. The majority of the birds investigated were nocturnal and diurnal raptors and came from "WildUmbria", a wildlife rescue centre in Central Italy. The initial clinical assessment revealed injuries mainly due to traumatic events. The E. coli isolates displayed significant resistance (p < 0.001) to ampicillin (85%) and amoxicillin/clavulanic acid (47%), which are widely used in veterinary and human medicine. Resistance to ciprofloxacin, cefotaxime, and ceftazidime showed values of 18%, 17% and 15%, respectively. Eight out of the hundred E. coli isolates (8%) were ESBL and seven displayed a multidrug resistance profile. Salmonella spp. was not isolated. Resistance to beta-lactams in all multidrug-resistant E. coli, including the presence of third-generation cephalosporins, highlights the need to increase wildlife monitoring studies to assess the potential risk to public health. The role of wildlife, including birds, in antimicrobial resistance is nowadays a speculative topic for the scientific community as they could be spreaders/sources of antimicrobial resistance genes. In this respect, we aimed to investigate the antimicrobial susceptibility of 100 commensal Escherichia coli strains, isolated from wild birds from an Umbrian rescue centre and admitted to the Veterinary Teaching Hospital of Perugia (Central Italy) mainly for traumatic injuries. The possible presence of Salmonella spp. and ESBL-producing E. coli was also estimated. The highest prevalence of resistance was observed for ampicillin (85%) and amoxicillin/clavulanic acid (47%), probably due to their extensive use in human and veterinary medicine. Seventeen out of the one hundred E. coli isolates (17%) displayed a multidrug-resistance profile, including the beta-lactam category, with the most common resistance patterns to three or four classes of antibiotics. Resistance to ciprofloxacin, cefotaxime and ceftazidime exhibited values of 18%, 17% and 15%, respectively. Eight out of the hundred E. coli isolates (8%) were ESBL and seven showed multidrug resistance profiles. Salmonella spp. was not isolated. Resistance to third-generation cephalosporins, also detected in long-distance migratory birds, suggests the need for monitoring studies to define the role of wild birds in antimicrobial resistance circuits. [ABSTRACT FROM AUTHOR]