Objective To explore the difference of pathogenic bacteria distribution, clinical characteristics and prognosis between severe purulent meningitis and moderate purulent meningitis in neonates, provide evidences for the early identification, timely treatment and prognosis evaluation of severe purulent meningitis. Methods 135 cases of neonatal purulent meningitis admitted in a hospital from October 2019 to October 2022 were selected and divided into the severe group and the moderate group based on the severity condition. Clinical data were collected retrospectively. Differences in clinical symptoms, auxiliary examinations, and prognosis between the two groups of neonates were analyzed. Results Among 135 cases of neonatal purulent meningitis, 60 cases were in the severe group and 75 cases in the moderate group. Compared with the moderate group, the proportions of premature infants, low birth weight infants, birth asphyxia history, and the incidence of premature rupture of membranes in the severe group were all higher (all P < 0.05); the incidence of poor responsiveness, convulsion, abnormal consciousness, tachypnea, tachycardia, hypoxemia, thrombocytopenia, liver function damage, and kidney function damage in the severe group were all significantly higher (all P < 0.05). Compared with the moderate group, the white blood cell count and protein concentration of cerebrospinal fluid in the severe group were higher, glucose concentration of cerebrospinal fluid were lower, and the incidence of complications was higher (all P < 0.05). Poor response, liver function damage, hypoxemia, the increase of cerebrospinal fluid protein concentration and the decrease of glucose concentration of cerebrospinal fluid were independent risk factors for neonatal severe purulent meningitis. Conclusion There are differences in clinical manifestations, laboratory examinations and complications between patients with severe purulent meningitis and moderate purulent meningitis. Early identification and active treatment of neonatal severe purulent meningitis can be achieved through clinical symptoms and laboratory examinations, enabling timely recognition and intervention.