Background <p>Viral encephalitis refers to the inflammation of the brain parenchyma caused by viral infection, usually manifested as fever, unconsciousness, seizures, and meningeal irritation symptoms. The non-specific clinical manifestations, combined with incomplete medical history, often lead to missed diagnoses and inappropriate treatments.</p> Case presentation <p>We present a case of Hepatitis B virus (HBV) encephalitis, manifesting as isolated left parietal lobe involvement. The patient is a chronic hepatitis B virus carrier who did not receive antiviral therapy. Upon onset, the main symptoms were unconsciousness, fever, and seizures. He was diagnosed with HBV encephalitis thru next-generation sequencing (NGS) testing of the cerebrospinal fluid (CSF). After antiviral treatment with entecavir and general symptomatic treatment, the patient’s clinical symptoms disappeared, and a follow-up brain MRI showed that the lesion had almost completely resolved.</p> Conclusions <p>Central nervous system (CNS) infections caused by HBV are incredibly uncommon in clinical practice. This case highlights that the clinical manifestations of HBV encephalitis are nonspecific and prone to being missed, while neuroimaging often reveals an isolated lesion. Early application of NGS for accurate pathogen diagnosis is crucial to reduce misdiagnosis.</p>