A case of mycoplasma encephalitis in newborn was reported. Sick children was admitted to hospital due to “yellow skin for 3 days”. Fever was observed during the course of illness, and the fever sustained for 22 days with the highest temperature of 39 ℃ after admission to the hospital. The examination of cerebrospinal fluid showed that the white blood cell count and the protein quatification level were obviously increased, and yet the glucose level was obviously decreased. Because of the poor effect from neonatal bacterial meningitis treatment, cerebrospinal fluid was taken for high-throughput gene detection of infectious pathogens, and Ureaplasma urealyticum was detected. Therefore, the patient was diagnosed as U. urealyticum infection. U. urealyticum is the main pathogen of neonatal mycoplasma infection, and the infection was mainly from the vertical transmission of intrauterine infection. The clinical manifestations and spinal fluid changes of mycoplasma encephalitis are pretty similar to those of neonatal bacterial meningitis. The Clinicians should pay attention to the etiological diagnosis, and macrolides can be selected for treatment.