Abstract: Objective To explore the effect of early prone position ventilation on children with sepsis and acute respiratory distress syndrome(ARDS). Methods Forty-two children with sepsis and ARDS who were admitted to the Pediatrics Department of Huzhou Central Hospital from January 2017 to December 2019 were selected, and they were randomly divided into observation group and control group, 21 cases of each. The two groups of children on the basis of conventional tracheal intubation and mechanical ventilation, the prone position ventilation strategy for both groups were adopted. The children of control group received prone ventilation within 24 hours and later of starting MV, while the children in the observation group performed prone ventilation within 6 hours of starting MV. The related indicators and complications were compared between the two groups. Results Compared with the control group, the observation group could stabilize heart rate faster [(96.3±6.4)beats/min vs.(109.6±10.1)beats/min], reduce airway platform pressure [(17.5±5.5)cm H₂O vs.(24.65±4.1)cm H₂O], increase arterial oxygen partial pressure significantly [(109.8±24.7)mm Hg vs.(67.5±22.8)mm Hg] and better improve the oxygenation index(114.2±20.6 vs. 89.1±17.2), as well as obviously shorten that mechanical ventilation time of tracheal intubation of children [(7.0±0.8)d vs.(11.6±1.8)d], improve the cure rate(95.23% vs. 66.67%), the differences were statistically significant(all P<0.05). However, the incidence of related complications in the two groups no statistically significant differences(all P>0.05). Conclusion The early prone position ventilation can significantly improve oxygenation index of septic children complicated with ARDS, stabilize heart rate faster, reduce airway platform pressure, shorten mechanical ventilation time of tracheal intubation and improve cure rate, but has no significant increase in which is worthy of clinical promotion.