Simple SummaryListeria monocytogenesis a widespread bacterium in nature thanks to its broad pH range stability as well as toleration of salt conditions up to 20% and temperatures ranging from −0.4 to 45 °C. The bacterium causes infection both in animals and humans, with variable and sometimes fatal disease manifestations. We isolatedL. monocytogenesfrom a stranded loggerhead sea turtle (Caretta caretta) that perished briefly after being rescued due to the lesions in many internal organs. Our findings underline how the sea turtle and its marine environment should be considered a source ofL. monocytogenescontamination. This is important, given zoonotic transmission either through contact with animals or via contaminated food, as well as in the light of the migratory behavior ofCaretta caretta.AbstractListeria monocytogenesis an ubiquitous pathogen isolated from different host species including fish, crustaceans, and molluscs, but it is rarely a pathogenic microorganism to marine reptiles. In particular, only two cases of fatal disseminated listeriosis have been described in the loggerhead sea turtle (Caretta caretta). In this study, we describe a lethal case ofL. monocytogenesinfection in a loggerhead sea turtle. The turtle was found alive, stranded on a beach in North-eastern Italy, but perished soon after being rescued. The autoptic examination revealed that heart, lung, liver, spleen, and urinary bladder were disseminated with multiple, firm, 0.1–0.5 mm sized, nodular, white-green lesions. Microscopically, these lesions corresponded with heterophilic granulomas with Gram+ bacteria within the necrotic center. Furthermore, the Ziehl–Neelsen stain was negative for acid-fast organisms. Colonies isolated from heart and liver were tested through MALDI-TOF for species identification, revealing the presence ofL. monocytogenes. Whole Genome Sequencing onL. monocytogenesisolates was performed and the subsequent in silico genotyping revealed the belonging to Sequence Type 6 (ST 6); the virulence profile was evaluated, showing the presence of pathogenicity islands commonly observed in ST 6. Our results further confirm thatL. monocytogenesshould be posed in differential diagnosis in case of nodular lesions of loggerhead sea turtles; thus, given the zoonotic potential of the microorganism, animals should be treated with particular caution. In addition, wildlife animals can play an active role as carriers of possibly pathogenetic and virulent strains and contribute to the distribution ofL. monocytogenesin the environment.