We investigated if serial domiciliary measures of spirometry were sensitive at detecting subtle effects of beta-2 blockade associated with bisoprolol in (n = 17) patients with COPD. After a two-week run in on inhaled corticosteroid (ICS) and long acting beta-2 agonist (LABA): beclometasone/formoterol 100/6 µg, patients' started additional a long acting muscarinic receptor antagonist: (LAMA) Tiotropium 18 µg, with concomitant weekly dose titration of bisoprolol: 1.25-2.5-5 mg. After a further week of bisoprolol 5 mg, they were stepped back down to (ICS/LABA) for one week. Mean age was 64 years, mean FEV1 52% predicted, and mean FEV1/FVC ratio of 0.46. Compared to baseline am FEV1 of 1.38 L (95% CI 1.14-1.61 L), both ICS/LABA/LAMA and ICS/LABA in conjunction with bisoprolol showed statistically significant mean falls of 100 ml (1.28 L, 95% CI 1.03-1.53 L), and 120 ml, respectively (1.26 L, 95% CI 1.01-1.51 L); equalling and exceeding the MCID of 100 ml, respectively. These changes were disconnected from symptoms, reliever use and oxygen saturation.