Streptococcus sanguinis meningoencephalitis is a rare disease， and rapid diagnosis of Streptococcus sanguinis meningoencephalitis is critical for effective clinical management of this disease. However， current diagnostic techniques are not effective for the early diagnosis of this disease. At present， metagenomic next-generation sequencing of cerebrospinal fluid is a promising method for the early diagnosis of central nervous system infection. As far as we know， there are few reports on the application of metagenomic next-generation sequencing of cerebrospinal fluid in the diagnosis of Streptococcus sanguinis meningoencephalitis. This article reports a case of Streptococcus sanguinis meningoencephalitis in a male patient aged 45 years， with no apparent trigger before disease onset. Routine examinations， including Gram staining and cerebrospinal fluid culture， did not identify bacterial infection； however， Streptococcus sanguinis was detected in cerebrospinal fluid bymetagenomic next-generation sequencing. This case report suggests that metagenomic next-generation sequencing of cerebrospinal fluid can help with the diagnosis of unexplained meningoencephalitis in clinical practice.