Background/Objectives: Healthcare-associated infections (HAIs), including sepsis, represent a major challenge in clinical practice owing to their impact on patient outcomes and healthcare systems. Large language models (LLMs) offer a potential solution by analyzing clinical documentation and providing guideline-based recommendations for infection management. This study aimed to evaluate the performance of LLMs in extracting and assessing clinical data for appropriateness in infection prevention and management practices of patients admitted to an infectious disease ward. Methods: This retrospective proof-of-concept study analyzed the clinical documentation of seven patients diagnosed with sepsis and admitted to the Infectious Disease Unit of San Bortolo Hospital, ULSS 8, in the Veneto region (Italy). The following five domains were assessed: antibiotic therapy, isolation measures, urinary catheter management, infusion line management, and pressure ulcer care. The records, written in Italian, were anonymized and paired with international guidelines to evaluate the ability of LLMs (ChatGPT-4o) to extract relevant data and determine appropriateness. Results: The model demonstrated strengths in antibiotic therapy, urinary catheter management, the accurate identification of indications, de-escalation timing, and removal protocols. However, errors occurred in isolation measures, with incorrect recommendations for contact precautions, and in pressure ulcer management, where non-existent lesions were identified. Conclusions: The findings underscore the potential of LLMs not merely as computational tools but also as valuable allies in advancing evidence-based practice and supporting healthcare professionals in delivering high-quality care.