Antimicrobial peptides, which are crucial effectors of innate immunity, are a promising substitute for antibiotics. The piscidin family is a group of fish-derived antimicrobial peptides that have potent antimicrobial activity and participate in the innate immune response. Here we describe a novel piscidin-like peptide called cerocin from the black sea bass (Centropristis striata), which is a highly valued marine teleost in both commercial and recreational fisheries worldwide. The full-length cDNA of cerocin consists of 567 base pairs, including 5' and 3' untranslated regions of 61 and 209 base pairs, respectively. The active peptide consists of 20 amino acids that form an amphipathic α-helix structure. Cerocin showed highest identity with the cardinalfish (Ostorhinchus fasciatus) piscidin (52%). Phylogenetic tree demonstrated that the cerocin clustered with dicentracin of Liparis tanakae and Perca flavescens. It showed tissue-specific distribution patterns and was predominantly expressed in the gill. After challenge with Vibrio harveyi, C. striata showed time- and tissue-dependent expression of the cerocin gene. Finally, a cerocin peptide was synthesized, and it exerted broad-spectrum antimicrobial activity against a number of bacterial strains, especially Gram-positive pathogens. Analysis of the killing kinetics revealed that the cerocin peptide had a rapid bactericidal effect on the bacteria. Collectively, these data suggest that the piscidin-like cerocin might play a vital role in the immune response of C. striata, and further studies of this gene may provide insight into the innate immune system of this species.