【Abstract】 Objective To investigate the effect of early mechanical ventilation combined with nitric oxide inhalation on neonatal severe pneumonia. Methods Eighty patients with severe pneumonia were enrolled in our hospital from January 2012 to May 2017. All children were randomly divided into observation group and control group (n = 40). The patients in the control group were treated with early mechanical ventilation. The patients in the observation group were treated with early mechanical ventilation combined with NO inhalation. The respiratory function indexes and blood gas indexes of the two groups were recorded before and 1h, 6h and 24h after treatment respectively. Of the lung function indicators and severe pneumonia related to the disappearance of clinical signs of time. Results The levels of FiO2 and OI at 6 and 24 hours after treatment were significantly lower than those before treatment at 1, 6 and 24 hours after treatment, and the a / A at 1, 6 and 24 hours after treatment was significantly higher than that before treatment (P＜005). The MAP, FiO2, OI and a / A of the observation group were statistically significant at 6 and 24 hours after treatment (P＜005), and the difference was statistically significant (P＜005). PaO2 and pH were significantly higher than those before treatment, and PaCO2 was significantly lower than that before treatment (P＜005). The children in the observation group had 6,24 h after treatment (P＜005). The levels of FVC, FEV1 and PEF in the observation group were significantly lower than those in the control group (P＜005), and the difference was statistically significant (P＜ 005). The time of disappearance of clinical signs such as triad, pulmonary rales, fever, cyanosis and nasal flap were significantly higher than those in the control group (P＜005), and the difference was statistically significant (P＜005). The duration of mechanical ventilation in the observation group was significantly shorter than that in the control group, the difference was statistically significant (P＜005). There was no significant difference in bleeding time, coagulation time and platelet count between the observation group and the control group (P＞ 005). Conclusion Early mechanical ventilation combined with NO can significantly improve the respiratory function and blood gas index of children, and significantly improve the lung function and severe pneumonia related clinical signs, and no side effects of prolonged clotting, has a certain clinical value.