Abstract Background There is accumulating evidence that oxidative stress plays an important role in the pathophysiology of chronic obstructive pulmonary disease (COPD). One current hypothesis is that the increased oxidant burden in these patients is not adequately counterbalanced by the lung antioxidant systems. Objective To determine the levels of oxidised human serum albumin (HSA) in COPD lung explants and the effect of oxidation on HSA degradation using an ex vivo lung explant model. Methods Parenchymal lung tissue was obtained from 38 patients (15F/23M) undergoing lung resection and stratified by smoking history and disease using the GOLD guidelines and the lower limit of normal for FEV 1 /FVC ratio. Lung tissue was homogenised and analysed by ELISA for total levels of HSA and carbonylated HSA. To determine oxidised HSA degradation lung tissue explants were incubated with either 200 μg/ml HSA or oxidised HSA and supernatants collected at 1, 2, 4, 6, and 24 h and analysed for HSA using ELISA and immunoblot. Results When stratified by disease, lung tissue from GOLD II (median = 38.2 μg/ml) and GOLD I (median = 48.4 μg/ml) patients had lower levels of HSA compared to patients with normal lung function (median = 71.9 μg/ml, P