Introduction: Nocardiosis is an unusual infection caused by aerobic gram-positive bacteria in the genus Nocardia. Infections resulting from Nocardia species are frequent in immunosuppressive patients. Weakened immune systems caused by human immunodeficiency virus infection, diabetes, cancer, and other conditions such as chronic lung disease, renal failure, etc, are the main risk factors for nocardiosis. Central nervous system (CNS) nocardiosis has been reported to represent similar to 2% of all and to be present in 15% to 50% of patients with systemic infection. The patient in our case had an isolated CNS nocardiosis caused by Nocardia terpenica infection, a rare reclassified Nocardia pathogen of CNS nocardiosis. Case: We here present a 54-year-old Chinese male with a fever and headache for 15 days who showed positive meningeal irritation signs. Magnetic resonance imaging showed the right trigone of the lateral ventricular choroid plexitis and diffused leptomeningeal meningitis involving the bilateral cerebral hemisphere, cerebellar hemisphere, and brain stem. The patient was quickly diagnosed with CNS Nocardia infection by next-generation sequencing within 48 hours after admission. Meanwhile, the diagnosis was validated by Nocardia-positive staining in cerebral spinal fluid culturing. The patient was given trimethoprim-sulfamethoxazole, and his symptoms recovered after 3 days. Conclusions :In this case, the clinical, radiological, and microbiological findings highlight the importance of suspecting Nocardia as the potential pathogen in patients with central nervous system inflammation of doubted immune incompetence. In addition, next-generation sequencing as an effective test is also highly recommended for suspicious CNS infection patients to perform a rapid diagnosis and treatment.