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To evaluate the recently discovered long pentraxin PTX3 in plasma of critically ill patients and to compare it with the classic short pentraxin C-reactive protein and with other indicators of inflammation.A cohort study on plasma samples.Medical intensive care unit (ICU) of the University Hospital of Basel.A total of 101 consecutive critically ill patients admitted to the medical ICU.Venous blood samples were routinely obtained at entry, on day 2, and at discharge or before death.Plasma samples were obtained from 101 consecutive critically ill patients admitted to the ICU with systemic inflammatory response syndrome, sepsis, or septic shock. PTX3 plasma levels were measured by enzyme-linked immunosorbent assay. PTX3 was elevated in critically ill patients, with a gradient from systemic inflammatory response syndrome to septic shock. PTX3 levels correlated with clinical scores reflecting severity of disease (e.g., Acute Physiology and Chronic Health Evaluation II:p = .00097). In addition, high levels of PTX3 were associated with unfavorable outcome.The long pentraxin PTX3 is elevated in critically ill patients and correlates with severity of disease and infection. Compared with the short pentraxin C-reactive protein, PTX3 may be a more direct indicator of tissue involvement by inflammatory and infectious processes.