Murine (m) Siglec-E and mSiglec-F are recently discovered murine sialic acid-binding Ig-like lectins with tyrosine-based inhibitory signaling motifs. They are postulated to be the orthologs of human (h) siglec-7, -8 or -9 and siglec-5, respectively. We report here the first detailed characterization of mSiglec-E, and compare its expression pattern with mSiglec-F. Similar to hSiglec-7, mSiglec-E preferred alpha 2-8-linked disialic acid over alpha 2-3- and alpha 2-6-linked sialic acids. Using a specific Ab, FACS analysis demonstrated that mSiglec-E was expressed mainly on neutrophils in blood and their immature precursors in bone marrow. mSiglec-E was present on peritoneal cavity macrophages and on subsets of mature NK cells and splenic dendritic cells. mSiglec-E was also found ona novel population of peritoneal cavity B-1a-like cells and a subset of splenic B cells enriched in transitional T2 and marginal zone B cells. In striking contrast to mSiglec-E, mSiglec-F was expressed predominantly on eosinophils in blood and their precursors in the bone marrow. The distinct and largely non-overlapping expression profiles of mSiglec-E and mSiglec-F suggest that they play non-redundant roles in the innate immune system. mSiglec-E is likely to modulate the functions of several types of effector cells, whereas mSiglec-F is likely to be more restricted to eosinophil biology.