The activation of leukocytes by bacterial cell wall lipopolysaccharide (LPS) contributes to the pathogenesis of septic shock. It is well established that, in the presence of plasma LPS‐binding protein (LBP), LPS binds with high affinity to CD14. The binding of LPS to CD14 has been associated with the activation of cells, although available evidence indicates that CD14 itself does not transduce intracellular signalling. The physiological function of this interaction is to promote host defense mechanisms of cells to combat the infection and clear LPS from the circulation. At higher concentrations of LPS, however, the activation of cells can take place in the absence of LBP and CD14, presumably through a distinct low‐affinity signalling LPS receptor. On the evidence published by us and others, we propose that in neutrophils, and possibly other leukocytes, L‐selectin can act as a low‐affinity LPS receptor.