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To measure serum thrombopoietin levels and to investigate their relationship with platelet counts and other potential determinants in septic patients.Prospective study comparing septic patients and healthy volunteers.General intensive care units in two tertiary university hospitals.A total of 152 consecutive septic patients (69 with sepsis, 24 with severe sepsis, and 59 with septic shock). Twenty-two healthy volunteers served as control subjects. Sepsis severity was determined by grading septic patients in those having sepsis, severe sepsis, and septic shock.None.After blood sampling, platelet counts, and serum thrombopoietin, interleukin-6 and C-reactive protein levels were measured. Platelets did not decrease in patients with sepsis, but they significantly decreased in patients with severe sepsis and septic shock (p < .01 vs. controls and sepsis). In contrast, thrombopoietin levels (median [range]) increased in patients with sepsis (159 [34–1272] pg/mL) compared with controls (57 [33–333] pg/mL, p < .001), exhibiting further significant increase in patients with severe sepsis and septic shock (461 [73–1550] and 522 [45–2313] pg/mL, respectively, p < .001 vs. sepsis). In multiple regression analysis, thrombopoietin levels were independently related only to sepsis severity (higher in patients with increased sepsis severity, p < .001) and platelet counts (higher in patients with lower platelet counts, p = .004). Sepsis severity accounted for most of the variance explained by the model. Thrombopoietin was significantly related to interleukin-6 (r2 = .26) and C-reactive protein (r2 = .37, p < .001 for both). In serial measurements, interleukin-6 peak values constantly preceded those of thrombopoietin, whereas peaks in thrombopoietin levels coincided with clinical episodes of septic shock.Sepsis severity is the major determinant of elevated thrombopoietin levels in septic patients, whereas platelet count is a secondary determinant. Thrombopoietin represents a potential marker of sepsis severity.