Blood-contacting biomaterials may activate the complement cascade, thus promoting leukocyte adhesion to the biomaterial surface. We hypothesize that the extent of complement activation is modulated by biomaterial formulation and the presence of fluid shear stress. To investigate this hypothesis, we tested base poly(etherurethane ureas) formulated with or without Santowhite antioxidant, a nucleophilic additive. We found that adherent leukocyte densities decreased with increasing shear stress. Moreover, leukocyte adhesion was decreased significantly further by Santowhite additive under shear stress but not under static conditions. Monocytes showed a higher propensity for adhesion than did neutrophils under shear and static conditions. Under static conditions, adherent cells on the Santowhite-containing polyurethane had a slightly more activated morphology than those on the base polyurethane. Cell adhesion under shear stress was significantly decreased when C3 or fibronectin was depleted from the suspension medium. Santowhite additive increased Factor B adsorption to the test surface while shear stress increased Factor H adsorption. The combination of Santowhite additive and shear stress increased the adsorption of both Factor B and Factor H and the serum protein S-terminal complement complex levels, but it did not further increase the state of activation of adherent cells. We conclude that leukocyte adhesion on poly(etherurethane urea) surfaces is sensitive to the levels of shear stress and that both C3 and fibronectin are required to maintain adhesion in the presence of shear stress. The low state of cellular activation and increased Factor H adsorption may explain the decreased adherent leukocyte density on the Santowhite-containing polyurethane.