Previously proposed markers for the differentiation of non-infectious SIRS and sepsis such as CRP (AUC = 0.57; 95% CI: 0.47–0.68), IL-6 (AUC = 0.63; 95% CI: 0.52–0.74) and PCT (AUC = 0.55; 95% CI: 0.34–0.56) performed worse than the model developed in the RF approach when applied to the validation dataset. This evidence concerns the gene IL6 and systemic inflammatory response syndrome.