Significance Pseudomonas aeruginosa , a versatile bacterium that lives in environmental habitats and causes life-threatening opportunistic infections, uses quorum sensing to coordinate gene expression. The lasR gene, which encodes a quorum-sensing regulator, is often found to have loss-of-function mutations in clinical isolates. Interestingly, LasR− strains have high activity of the oxygen-sensitive transcription factor Anr in microoxic conditions. This report identifies and characterizes an Anr-regulated microoxic hemerythrin that binds oxygen. We show that both anr and mhr are critical to fitness in microoxia and that these genes uniquely benefit LasR− strains in biofilms grown in normoxia. Our data suggest that the success of P. aeruginosa in chronic infections is in part through its propensity to lose LasR functionality resulting in increased microoxic fitness.