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Introduction: Plesiomonas shigelloides is a gram-negative bacillus causing foodborne infection due to contaminated seafood leading to gastroenteritis and dysentery. Instances of neonatal infection attributed to Plesiomonas shigelloides are exceedingly rare, and available literature is sparse, with only 15 reported cases to our knowledge. Central nervous system (CNS) involvement is reported, presenting severe meningoencephalitis in some cases., Case Presentation: In this study, we report the case of a newborn with a clinical presentation of neonatal sepsis and central nervous system (CNS) involvement with meningoencephalitis caused by Plesiomonas shigelloides. Moreover, we review literature about this rare form of neonatal infection. During recovery, the baby underwent various laboratory tests and neurological diagnostic images (cerebral ultrasound, computer tomography and brain magnetic resonance), and received oxygen support, antibiotics, and anti-seizure treatment. Cerebral involvement in our patient was complicated by an extended abscess, cerebral arteritis, obstructive hydrocephalus, and a stroke which required multiple surgical interventions including drainage and a neurosurgical lobectomy. Gradual improvement in the general clinical condition of the child was observed, and he was discharged with a comprehensive follow-up program of clinical assessments, neurosurgical evaluations, neuroimaging monitoring, and physiotherapeutic care., Conclusion: We present a case of neonatal sepsis and neurological involvement caused by Plesiomonas shigelloides which resulted in a positive outcome despite severe neurological complications. This case contributes valuable additional data on the clinical course and radiological features of neonatal CNS involvement caused by this pathogen which is exceedingly rare and poorly described in the literature. This study also underscores the importance of targeted interventions and proposes specific recommendations for these unique cases., Competing Interests: Declarations. Ethical approval and consent to participate: This study protocol was reviewed and approved by the Pediatric Ethics Committee of Tuscany Region. Written informed consent was obtained from the parents of the patient for publication of the details of their medical case and any accompanying images. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)