Background <p>Pneumonia is a major health problem and the most important causes of mortality in all age groups worldwide. We investigated new automation technology to detect plasma biomarkers, including thrombinantithrombin complex (TAT), α2-plasmininhibitor-plasmin complex (PIC), soluble thrombomodulin (sTM), and tissue plasminogen activator-inhibitor complex (t-PAI·C), and evaluated their diagnostic performance and prognostic value for severe pneumonia patients.</p> Methods <p>We collected 414 patients date with pneumonia. sTM, t-PAI·C, TAT, PIC were measured by qualitative chemiluminescence immunoassay performed on HISCL analyzers. Other laboratory tests were evaluated on the day of non-severe pneumonia and severe pneumonia diagnosis.</p> Results <p>There were significant differences in sTM, t-PAI·C, TAT, PIC (<i>p</i> &lt; 0.0001), WBC (<i>p</i> = 0.023), PCT (<i>p</i> = 0.007) and IL-6 (<i>p</i> = 0.002) between the severe pneumonia and non-severe pneumonia groups, Logistic regression analysis showed that sTM (<i>p</i> = 0.001), t-PAI·C (<i>p</i> = 0.001), TAT (<i>p</i> = 0.022), PIC (<i>p</i> = 0.000) and APTT (<i>p</i> = 0.013) were independent risk factors for severe pneumonia. Logistic regression analysis showed that t-PAI·C (<i>p</i> = 0.006) was an independent risk factor for hospital mortality in severe pneumonia. The AUC of sTM combined with t-PAI·C, TAT and PIC on diagnosis of patients with severe pneumonia was 0.868 (95% CI: 0.837, 0.899). Kaplan-Meier survival analysis with a log-rank test showed the in-hospital death rate of severe pneumonia was higher in the high TAT (≥ 5.58ng/mL) level than in group with low TAT (&lt; 5.58ng/mL) level (log rank &lt; 0.029). The same trend with high t-PAI·C was also found in severe pneumonia patients (log rank &lt; 0.021).</p> Conclusions <p>The thrombosis markers are helpful for the diagnosis and prognostic assessment of severe pneumonia.</p>