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Objective This study aimed to examine the characteristics of blood lactate in neonates undergoing mechanical ventilation in Tibet. Methods We recruited 67 neonates undergoing mechanical ventilation in Naqu People’s Hospital as the plateau observation group and 94 neonates undergoing mechanical ventilation in Shengjing Hospital as the control group. We analyzed the differences in lactate levels between the two groups. Results The lactate clearance rates of neonates with asphyxia and those with respiratory distress syndrome were significantly lower in the plateau group than in the control group. Lactate levels in neonates who died in the plateau group were significantly higher and the lactate clearance rate was significantly lower than those in neonates who survived. The cut-off point for the lactate clearance rate at 6 hours for predicting mortality was 6.09% in the plateau group. Conclusion The lactate clearance rate of neonates on mechanical ventilation in the plateau area is lower than that in neonates in the non-plateau area. The lactate clearance rate at 6 hours is important for evaluating the prognoses of critical neonates in plateau areas.