A partial clone coding for a two-WAP domain protein was isolated from a Litopenaeus vannamei haemocytes cDNA library. The complete sequence was obtained by RACE, and the full-length cDNA sequence is 0.8 Kb long and encodes for a 116-amino acid protein. The domain composition is similar to the mammalian WFDC5 (WAP four disulfide core) and secretory leukocyte proteinase inhibitor (SLPI). Modifications in expression were determined by real-time PCR, after injection of Vibrio alginolyticus, suggesting its participation in the shrimp immune response. Structural and phylogenetic analyses showed close similarity between shrimp and mammalian SLPI, indicating a probable common ancestor. This is the first report of a mammalian SLPI-like protein in an invertebrate.