Objective? To study the effects of nasal high-flow humidification oxygen therapy and continuous positive airway pressure on blood gas indicators and inflammatory factors of neonates with pneumonia. Methods A total of 58 children with neonatal pneumonia admitted to CITIC Huizhou Hospital from January 2018 to January 2021 were selected and divided into the control group (29 cases) and the treatment group (29 cases) according to the random number table method. Children in the control group were treated with continuous positive airway pressure through the nose, and children in the treatment group were treated with nasal high-flow humidification oxygen therapy, when the blood gas analysis was basically normal, they were stable for 12 to 24 hours and then changed to nasal catheter oxygen inhalation, and continued to observe for 7 d after treatment. The clinical symptoms improvement , blood gas indexes and inflammatory factor levels before and 24 h after treatment, and the occurrence of complications after treatment of children were compared between the two groups. Results Compared with before treatment, the heart rate (HR), respiratory rate (RR), arterial partial pressure of carbon dioxide (PaCO2), serum interleukin-6 (IL-6) , C-reactive protein (CRP) and procalcitonin (PCT) levels reduced significantly, and the treatment group was significantly lower than the control group; 24 h after treatment, arterial blood oxygen partial pressure (PaO2), arterial/alveolar oxygen partial pressure (a/APO2) and the neonatal critical case score of the treatment group increased significantly, and the treatment group was significantly higher than the control group; the total incidence of complications in the treatment group was significantly lower than that of the control group (all P <0.05). Conclusion? Nasal high-flow humidification oxygen therapy can effectively improve the blood gas level of the children with neonatal pneumonia, while neonatal inhibiting the release of serum inflammatory factors and reducing the incidence of complications.