A library of secondary metabolites from microorganisms was screened to identify novel inhibitors against lipopolysaccharide (LPS), a strong stimulant of innate immunity. Novel cyclic peptides, ogipeptin A, B, C and D, were identified in the culture broth of the marine bacterium Pseudoalteromonas sp. SANK 71903. These compounds blocked LPS binding to the cluster of differentiation 14 (CD14) in vitro with IC50 values of 4.8, 6.0, 4.1 and 5.6 nm, respectively, and attenuated tumor necrosis factor-α secretion from LPS-stimulated macrophage-like cells. These compounds also displayed antimicrobial activity against Escherichia coli with minimum inhibitory concentrations ranging from 0.25 μg ml-1 to 1 μg ml-1. Thus, novel antibiotics that inhibited LPS-induced innate immune reactions were identified in this study.