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Simple Summary: Gram negative organisms are frequently isolated from Caretta caretta and may contribute to the dissemination of antimicrobial resistance. In this study, commensal bacteria isolated from oral and cloacal samples of 98 healthy C. caretta were compared to clinical isolates isolated from the wounds of 102 injured animals, in order to investigate the presence of antimicrobial resistance bacteria in free-living loggerheads from the Adriatic Sea. A total of 410 bacteria were cultured and differences were noted in the isolated genera, as some of them were isolated only in healthy animals, while others were isolated only from injured animals. When tested for susceptibility to antimicrobials, clinical isolates showed highly significant differences in the antimicrobial resistance rates vs. commensal isolates for all the drugs tested, except for doxycycline. The detection of high antimicrobial resistance rates in loggerhead sea turtles is of clinical and microbiological significance since it impacts both the choice of a proper antibiotic therapy and the implementation of conservation programs. Gram negative organisms are frequently isolated from Caretta caretta turtles, which can act as reservoir species for resistant microorganisms in the aquatic environment. C. caretta, which have no history of treatment with antimicrobials, are useful sentinel species for resistant microbes. In this culture-based study, commensal bacteria isolated from oral and cloacal samples of 98 healthy C. caretta were compared to clinical isolates from the wounds of 102 injured animals, in order to investigate the presence of AMR bacteria in free-living loggerheads from the Adriatic Sea. A total of 410 isolates were cultured. Escherichia coli and genera such as Serratia, Moraxella, Kluyvera, Salmonella were isolated only in healthy animals, while Acinetobacter, Enterobacter, Klebsiella and Morganella were isolated only from the wounds of the injured animals. When tested for susceptibility to ampicillin, amoxicillin + clavulanic acid, ceftazidime, cefuroxime, gentamicin, doxycycline, ciprofloxacin and enrofloxacin, the clinical isolates showed highly significant differences in AMR rates vs. commensal isolates for all the drugs tested, except for doxycycline. The detection of high AMR rates in loggerheads is of clinical and microbiological significance since it impacts both the choice of a proper antibiotic therapy and the implementation of conservation programs. [ABSTRACT FROM AUTHOR]