Neutrophils are the most prominent cell in the immune system, accounting for 70% of circulating leukocytes, and acting as the first line of defense against various invading pathogens. For example, neutrophils engage in phagocytosis, degranulation, and neutrophil extracellular trap formation to respond to pathogens. Pseudomonas aeruginosa is a Gram-negative bacterium that readily forms biofilms (i.e., high-density bacterial clusters attached to surfaces) to provide protection from the host immune system, antibiotic treatment, and antimicrobial agents. Neutrophils are essential to clear P. aeruginosa biofilms and infections through the actions of antimicrobial proteins and peptides. In this study, we evaluated proteome remodeling of the host following exposure of neutrophils (differentiated from HL-60 cells) to P. aeruginosa biofilms.