Objective: To determine the activation of nuclear factor-kappa B in peripheral blood CD14+ monocyte/macrophages and CD3+, CD4+, and CD8+ T cells in children with sepsis. Design: Observational study. Setting: University hospital. Patients: Twenty-six children with sepsis (nine females and 17 males, aged between 10 days and 15 yrs; median, 4.3 yrs) on admission to our hospital between August 1999 and November 2005. Interventions: None. Measurements and Main Results: The percentages of peripheral blood CD14+ monocyte/macrophages and CD3+, CD4+, and CD8+ T cells exhibiting nuclear factor-kappa B activity were determined by flow cytometry. In addition, relationships among the degree to which nuclear factor-kappa B was activated, serum levels of cytokines (interferon-gamma, tumor necrosis factor-alpha, interleukin-2, interieukin-4, interleukin-6, and interleukin-10), and clinical variables were analyzed. The percentage of cells exhibiting nuclear factor-kappa B activity was increased among CD14+, CD3+, CD4+, and CD8+ cells in the sepsis group and was significantly higher among CD14+, CD3+, and CD4+ cells of the patients with severe sepsis (n = 9) than those of patients with nonsevere sepsis (n = 17). The percentage of cells exhibiting nuclear factor-kappa B activity was significantly higher among CD14+ cells than CD3+ cells in the patients with severe sepsis. In addition, this percentage was significantly higher among CD14+ cells than CD3+, CD4+, and CD8+ cells in septic patients who had positive blood cultures (n = 16). Serum interleukin-6 levels were correlated with the percentages of CD14+, CD3+, CD4+, and CD8+ cells exhibiting nuclear factor-kappa B activity, and serum IL-1 0 levels were correlated with the percentages of CD14+, CD3+, and CD4+ cells exhibiting nuclear factor-kappa B activity. Conclusions. Nuclear factor-KB in peripheral blood mononuclear cells was activated in children with sepsis and was related the severity of sepsis,