Activation of macrophages represents one of the initial events in innate immunity to intracellular infections. CD14 is expressed principally by cells of monocyte/macrophage lineage and plays a pivotal role in innate recognition of bacterial cell wall components, particularly lipopolysaccharides. We measured serum concentrations of soluble CD14 (sCD14) in serum samples obtained from 37 patients with brucellosis and 36 healthy controls. Serum levels of sCD14 were significantly increased in patients with brucellosis compared with those in healthy controls (P < 0.001). Re-analysis of serum samples after treatment in 25 patients demonstrated that treatment did not result in any significant decline in sCD14 levels. Despite a limited study population, these findings may implicate CD14 signaling as an important component of the initial anti-brucellar host response and suggest that activation of mononuclear phagocytic system is sustained even following effective treatment.