In this study, we have assessed β2AR-induced H2O2 generation in human airway epithelial cell lines as well as in primary healthy and asthma-diseased human small airway epithelial cells (SAEC) and for the first time, we reveal β2AR agonist and H2O2-induced S-sulfination of β2AR, suggesting that this over-oxidation of β2AR may contribute to lack of β2AR function seen in β2-agonist tachyphylaxis. Here, ADRB2 is linked to asthma.