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Objectives: To investigate whether stress hyperglycemia affects the production of the main pro- and anti-inflammatory cytokines and the 28-day hospital mortality in patients with severe sepsis., Methods: The study included 62 patients with severe sepsis, divided in three groups according to their glycemic profile within 24h after admission: patients with stress hyperglycemia (group SH, n=16), diabetes mellitus type II (group DM, n=27), and normal glucose levels (group NG, n=19). The serum levels of the cytokines TNF-alpha, IL-6, IL-10 and TGFbeta-1 were measured within 24h after admission., Results: A higher percentage of septic patients with stress hyperglycemia died compared to diabetic patients (43.7 vs. 14.8%) and group NG (43.7 vs. 5.2%). Group SH had higher SOFA score and levels of IL-6 and IL-10 than group DM and group NG. It also had higher levels of TNF-alpha than group DM but not group NG. There was no difference in the levels of TGFbeta-1 among the three groups. Non-survivors had higher levels of IL-10, no difference was detected for IL-6, TNF-alpha, IL-10/TNF-alpha ratio and TGFbeta-1. Interleukin-10 values, mean fasting glucose values and age were found as prognostic factors associated with outcome., Conclusions: Stress hyperglycemia is associated with increased cytokine production and an adverse clinical outcome in patients with severe sepsis.