A proinflammatory cytokine interleukin-6 (IL-6) plays an important role in the development, pathogenesis and outcome of SIRS, sepsis and septic shock. We have evaluated the role of the IL-6 gene polymorphisms in pediatric patients. A total of 421 consecutive pediatric patients admitted to the pediatric intensive care unit with fever, systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock, or multiple organ distress syndrome (MODS) were studied together with 644 healthy controls. DNA was isolated and two IL-6 gene polymorphisms (G-174>C and G-572>C) were analyzed. The frequencies of both analyzed variants differ significantly between the group of patients and healthy controls (p = 0.02 for G-174>C and p = 0.049 for G-572>C). In addition, genetic analysis of the G-174>C IL-6 gene variant revealed significant differences between the subgroup of febrile patients and subgroup of septic shock (p = 0.0319) and between the subgroup of SIRS and septic shock (p = 0.038). In both cases the negative genotype was CC. No statistically significant differences for the IL-6 gene polymorphism G-572>C were found between the groups of patients with different diagnosis. IL-6 gene polymorphisms G-174>C and G-572>C could be the predictors of risk of development and/or the predictors of the severity of sepsis in children.