Background <p>Rabies, a lethal viral encephalitis caused by Rabies virus (RabV), is transmitted via bites, scratches, or mucosal contact with infected animals, as well as through inhalation of aerosolized particles, ingestion of contaminated raw animal products, or transplantation of infected organs. It’s near-universal fatality, diverse transmission routes, and marked clinical variability significantly impede timely diagnosis, highlighting the demand for a rapid and precise diagnostic approach.</p> Methods <p>Single-center retrospective case series.</p> Results <p>This series reported three rabies cases admitted to the First People’s Hospital of Qinzhou: one without identifiable exposure and two with confirmed exposure histories. Clinical presentations were highly variable and diagnostically misleading. Application of Probe-Capture Metagenomics (pc-mNGS) to cerebrospinal fluid and blood samples enabled direct identification of RabV and concurrent detection of coexisting pathogens.</p> Conclusion <p>pc-mNGS demonstrates potential as a rapid, economical diagnostic tool capable of detecting RabV in specimens with low viral loads—such as blood and cerebrospinal fluid—from both exposed and unexposed individuals. Simultaneous identification of additional pathogens further supports its diagnostic utility.</p>