Cellular stress and inflammation contribute to the initiation and progression of a variety of pulmonary diseases. Endoplasmic reticulum (ER) stress and its main regulator GRP78 (glucose-regulated protein 78 kDa) appear to be involved in the pathogenesis of pulmonary diseases, and GRP78 was found to be a biomarker in a wide range of inflammatory diseases. The aim of this study was to investigate the relevance of serum GRP78 in pulmonary disorders.In this prospective cohort study, 78 consecutive patients with chronic obstructive pulmonary disease (COPD,n= 28), asthma (n= 38) or interstitial lung disease (ILD,n= 12) underwent measurement of serum GRP78 levels by ELISA.The mean age of patients was 59.8 ± 12.4 years, 48.7% were female. Patients with elevated GRP78 levels (> median) offered a significantly better oxygenation status (capillary pO2: 75.3 ± 11.7 mmHg vs. 67.8 ± 15.9 mmHg,p= 0.02). Significant correlations were observed between GRP78, on the one hand, and haemoglobin, high-sensitivity C-reactive protein (hs-CRP) and eosinophil counts, on the other hand (haemoglobin: Pearson’sr= −0.25, hs-CRP:r= 0.30, eosinophils:r= 0.63).Subsequently, we evaluated GRP78 measurements in function of severity stratifiers of the specific underlying pulmonary disease. ILD patients with a severe diffusion impairment (DLCO< 40% of predicted), exhibited a significant decrease in GRP78 levels (p= 0.01). In COPD and asthma, both characterized by obstructive ventilatory defects, a forced expiratory volume in one second (FEV1) <30% of predicted was accompanied by significantly lower GRP78 (p= 0.0075).In both obstructive and restrictive pulmonary disorders, GRP78 protein concentrations were reduced with increasing disease severity. These data suggest a prevalent role of GRP78 in the presently studied pulmonary disorders.