The impact of antibiotics on total endotoxemia and circulating tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 in 18 patients with severe bacteremic sepsis or septic shock due to gram-negative species was investigated. Endotoxemia, TNF-alpha, IL-6, and IL-8 were assayed before (H0) and 1 h (H1) and 4 h (H4) after the first antibiotic infusion. Endotoxemia decreased from H0 (median, 0.4 EU/mL; interquartile interval, 0.09-1.23) to H1 (median, 0.19 EU/mL; interquartile interval, 0.07-0.75; P = .03) and remained stable between H1 and H4 (median, 0.12 EU/mL; interquartile interval, 0.09-0.30; P = .4). IL-6 levels fell between H0 and H4 (P = .01) and between H1 and H4 (P = .03). IL-8 was higher at H0 than at H1 (P = .04) and at H4 (P = .01). These results suggest that endotoxemia is not increased by antibiotherapy of severe gram-negative bacteremia.