The PqsE enzyme plays a vital role in quorum sensing and virulence in Pseudomonas aeruginosa, yet its enzymatic function is unknown. Here, we identify the protein interaction network of PqsE as well as that of a catalytically dead variant, PqsE(D73A) in P. aeruginosa PA14. Our analyses identify proteins that interact with PqsE that are independent of and that depend on PqsE catalytic function. One such catalysis-independent interaction is with the quorum-sensing regulator, RhlR, consistent with our previous work. We also characterize the PqsE interaction network in a delta rhlR P. aeruginosa PA14 strain and identify additional proteins as PqsE-interactors.