Clinical manifestations, laboratory tests, imaging features, as well as treatment and prognosis of two cases of Ureaplasma parvum (U. parvum) meningitis in premature infants in a hospital were retrospectively analyzed, and provide evidence for early diagnosis and treatment. The main clinical symptom of two groups of premature infants was fever, and the efficacy of empirical antimicrobial therapy was not satisfactory. The metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid indicated U. parvum infection. After receiving azithromycin anti-infection therapy, conditions of two premature infants improved. They were followed up to 14 and 18 months old, respectively, and their neurobehavioral development was similar to that of normal children of the same age. The clinical symptoms of U. parvum meningitis in premature infants lack specificity. When conventional anti-infective therapy is ineffective, mNGS of cerebrospinal fluid can identify the pathogen. Azithromycin is effective, and the prognosis of premature infants with U. parvum meningitis is good.