Treatment of acute and chronic pulmonary infections caused by opportunistic pathogen Pseudomonas aeruginosa is limited by the increasing frequency of multidrug bacterial resistance. Here, we describe a novel adjunctive therapy in which administration of a mix of simple sugars - mannose, fucose, and galactose - inhibits bacterial attachment and lung damage, and potentiates standard antibiotic therapy. The sugar mixture inhibits adhesion of non-mucoid and mucoid P. aeruginosa strains to bronchial epithelial cells in vitro. In a murine pneumonia model, treatment with the sugar mixture alone diminishes bacterial dissemination to the subpleural alveoli, lung damage, and neutrophil- and IL-8-driven inflammatory responses. Remarkably, the sugars act synergistically with conventional antibiotics, beta-lactams and quinolones, to further reduce bacterial lung burden and lung damage in murine model of acute pneumonia, and, in an ex vivo infections of live trachea and lung tissues, to further reduce bacterial count. In ex vivo infections and in vitro host-free liquid bacterial culture, the sugars induce rapid but reversible formation of bacterial clusters that exhibit enhanced susceptibility to antibiotics compared to individual bacteria. These suggest a mechanism, at least in part dependent on host cell factor(s), by which the sugars potentiate the efficacy of antibiotics in vivo and ex vivo. Our findings show that sugar inhalation, an inexpensive and safe therapeutic, could be used in combination with conventional antibiotic therapy to more effectively treat P. aeruginosa lung infections.