OBJECTIVES In many pathological conditions, including high-risk surgery, the severity of the inflammatory response is related to the patient outcome. However, determining the patient inflammatory state presents difficulties, as markers are obtained intermittently through blood testing with long delay. RBC aggregation is a surrogate marker of inflammation that can be quantified with the ultrasound Structure Factor Size and Attenuation Estimator. The latter is proposed as a real-time inflammation monitoring technique for patient care. DESIGN Ten swine underwent a 90-minute cardiopulmonary bypass, and surveillance was maintained during 120 minutes in the postbypass period. To promote the inflammatory reaction, lipopolysaccharide was administrated two times prior to surgery in six of those swine (lipopolysaccharide group). During the whole procedure, the Structure Factor Size and Attenuation Estimator cellular imaging method displayed a RBC aggregation index (W) computed from images acquired within the pump circuit and the femoral vein. Interleukin-6, interleukin-10, C-reactive protein, haptoglobin, immunoglobulin G, and fibrinogen concentrations were measured at specific periods. MAIN RESULTS Compared with controls, the lipopolysaccharide group exhibited higher W within the pump circuit (p < 0.05). In the femoral vein, W was gradually amplified in the lipopolysaccharide group during cardiopulmonary bypass and the postbypass period (p < 0.05), whereas interleukin levels were higher in the lipopolysaccharide group but only at the end of cardiopulmonary bypass and beginning of postbypass (p < 0.05). CONCLUSIONS Continuous RBC aggregation monitoring can characterize the evolving inflammatory response during and after cardiopulmonary bypass. The Structure Factor Size and Attenuation Estimator is proposed as a real-time noninvasive monitoring technique to anticipate inflammation-related complications during high-risk surgery or critical care situations. Because RBC aggregation promotes vascular resistance and thrombosis, W could also provide early information on vascular disorders in those clinical situations.