High-throughput proteomics was used to determine the role of the fish liver in defense responses to bacterial infection, done using a rainbow trout (Oncorhynchus mykiss) model following infection with Aeromonas salmonicida, the causative agent of furunculosis. The vertebrate liver has multifaceted roles in innate immunity, metabolism, and growth; we hypothesize this tissue serves a dual function in supporting host defense in parallel to metabolic adjustments that promote effective immune function. While past studies have reported mRNA responses to A. salmonicida in salmonids, the impact of bacterial infectionon the liver proteome remains uncharacterized in fish.