The aim of this work was to study the expression and function of the innate immune receptor dectin-1 in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). We studied twenty-six patients with SLE not receiving immunosuppressive therapy, twenty-six patients with RA, and fifteen controls. We found that monocytes from SLE patients showed a diminished expression of dectin-1 compared to healthy controls, and an inverse correlation between percent of dectin-1(+) cells and the disease activity score was detected. In addition, cells from SLE patients showed an abnormal calcium flux response induced by dectin-1 ligands as well as an enhanced release of IL-1β, IL-6 and TNF-α, but not IL-23, upon dectin-1 engagement. Monocytes from patients with RA also showed a diminished expression, and a defective function of dectin-1. Our data suggest that dectin-1 receptor defects could contribute to the pathogenesis of autoimmune inflammatory conditions.