To determine whether hemofiltration (HF) can eliminate cytokines and complement components and alter systemic hemodynamics in patients with severe sepsis. Prospective observation study. Surgical intensive care unit of a university hospital. 16 patients with severe sepsis. Continuous zero-balanced HF without dialysis (ultrafiltrate rate 21/h) was performed in addition to pulmonary artery catheterization, arterial cannulation, and standard intensive care treatment. Plasma and ultrafiltrate concentrations of cytokines (the interleukins IL-1β, IL-6, IL-8, and tumor necrosis factor α) and of complement components (C3adesArg, C5adesArg) were measured after starting HF (t0) and 4 h (t4) and 12 h later (t12). Hemodynamic variables including mean arterial pressure (MAP), mean central venous pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac output were serially determined. During HF, cytokine plasma concentrations remained constant. However, C3adesArg and C5adesArg plasma concentrations showed a significant decline during 12-h HF (C3adesArg: t0=676.9±99.7 ng/ml vs t12=467.8±71,p<0.01; C5adesArg: 26.6±4.7 ng/ml vs 17.6±6.2,p<0.01). HF resulted in a significant increase over time in systemic vascular resistance (SVR) and MAP (SVR at t0: 669±85 dyne·s/cm5 vs SVR at t12: 864±75,p<0.01; MAP at t0: 69.9±3.5 mmHg vs MAP at t12: 82.2±3.7,p<0.01). HF effectively eliminated the anaphylatoxins C3adesArg and C5adesArg during sepsis. There was also a significant rise in SVR and MAP during high volume HF. Therefore, HF may represent a new modality for removal of anaphylatoxins and may, thereby, deserve clinical testing in patients with severe sepsis.