Pseudomonas aeruginosa is an opportunistic pathogen exhibiting higher resistance to commonly used antibiotics. Microbial resistance to antibiotics is a major problem that hinders attempts to control microbial infections. Quorum sensing inhibitors could help us solve such problem by repressing quorum sensing that controls the production of virulence factors in many pathogens including P. aeruginosa. In this study, the influence of tenoxicam, a non-steroidal anti-inflammatory drug, on quorum sensing in P. aeruginosa was characterized. Treatment of P. aeruginosa with tenoxicam decreased production of many virulence factors such as pyoverdin, rhamnolipids, pyocyanin, elastase, proteases, and hemolysins. Moreover, qRT-PCR revealed a significant reduction in expression of quorum sensing genes in tenoxicam-treated P. aeruginosa in comparison with untreated bacteria. Tenoxicam markedly reduced the capacity of P. aeruginosa to kill mice infection model. Mice injected with tenoxicam-treated P. aeruginosa exhibited higher survival rate as compared with those inoculated with untreated bacteria. Current data clearly demonstrate that tenoxicam has quorum sensing inhibitory effect on P. aeruginosa. Tenoxicam could play a role in reduction of Pseudomonas quorum sensing-dependant virulence factors production, and therefore affect its pathogenesis in the host. In summary, the current study suggests that tenoxicam could be used as adjuvant to antibiotics in the management of diseases caused by P. aeruginosa.