Leucine-rich repeat (LRR)-only proteins are involved in the innate immune responses as they mediate protein-ligand interactions. In the present study, three novel LRR-only proteins, CfLRRop-4, CfLRRop-5 and CfLRRop-6, were identified and characterized from Zhikong scallop Chlamys farreri. They all contained LRR motifs with consensus signature sequences of LxxLxLxxNxL or LxxLxLxxCxxL. All the mRNA transcripts of three CfLRRops were high abundant in hepatopancreas, gills and gonads, and their mRNA transcripts in hemocytes could respond to the stimulations of different microbes, including Vibrio anguillarum, Micrococcus luteus and Pichia pastoris. These three CfLRRops exhibited similar ligand binding and recognition characteristics as Toll-like receptors (TLRs) and NOD-like receptors (NLRs). The immune effectors, including tumor necrosis factor α, superoxide dismutase, catalase and lysozyme, varied significantly after the scallops were stimulated by recombinant LRR-only proteins. All these results indicated that LRR-only proteins are functionally differentiated and exhibit different immunomodulation activities on various downstream immune effectors.