<p>This study aims to evaluate the predictive value of the Lung Injury Prediction Score (LIPS) combined with serum markers including Krebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), von Willebrand factor (vWF), and interleukin-8 (IL-8) in predicting pediatric acute respiratory distress syndrome (pARDS) in critically ill children with severe pneumonia in the PICU. This study enrolled 97 children with severe pneumonia admitted to the PICU. They were classified into the pARDS group or non-pARDS group based on whether pARDS developed within 7 days of admission. LIPS and serum levels of KL-6, SP-D, vWF, and IL-8 were recorded and measured at PICU admission (T₁) and at the time of pARDS diagnosis (T₂). Additionally, 30 healthy children undergoing physical examination during the same period were included as the control group. At T₁, the LIPS, KL-6, SP-D, vWF, and IL-8 levels were significantly higher in the pARDS group compared to the non-pARDS and control groups (<i>P</i> &lt; 0.05). At T₂, the levels of LIPS, KL-6, SP-D, vWF, and IL-8 in the pARDS group were significantly higher than those at T₁ (<i>P</i> &lt; 0.01). Logistic regression analysis showed that LIPS, KL-6, SP-D, and vWF were independent risk factors for the occurrence of pARDS in children with severe pneumonia (<i>P</i> &lt; 0.05). The receiver operating characteristic curve demonstrated that the area under the curve for LIPS and its combination with the four serum biomarkers for predicting pARDS in children with severe pneumonia were 0.786 and 0.906, respectively. Sensitivity and specificity were 73.3% and 83.3% for LIPS, and 85.1% and 91.0% for the combination of LIPS and serum biomarkers. LIPS, KL-6, SP-D, and vWF exhibit good predictive value for pARDS in children with severe pneumonia, and the combined use of LIPS and these four serum markers provides the ultimate predictive performance.</p>