Background To enhance accuracy in evaluating prognosis and target therapy, there is a need for biomarkers in COPD. Yet, there are no reliable biomarkers that can differentiate between phenotypes of COPD. MFAP4 is a glycoprotein, co-localized with elastin and microfibrils in elastic fibres. We hypothesized that circulating MFAP4 reflects elastin degradation and thereby emphysema in COPD patients. Methods Plasma levels of MFAP4 (pMFAP4) were determined by ELISA in 74 Danish COPD patients from the multicentre ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points) study. Associations between log-transformed pMFAP4 levels and clinical outcomes were assessed by multiple regression analysis. Age, gender and current smoking were included as covariates. Results Levels of pMFAP4 associated significantly with GOLD stages and were significantly higher in GOLD IV than in II. LogpMFAP4 was positively correlated to percentage of low attenuation area on HRCT (LAA%) (β: 0.007, p<0.005). There was moreover a significant negative association between plasma logpMFAP4 and FEV1/FVC index (β:-0.007, p<0.05), reversibility (β:-0.6p<0.05). There was a significant interaction between gender and BMI and Fat Free Mass Index respective (FFMI), showing a significant negative association between MFAP4 and BMI (β:-0.03, p<0.01) and FFMI (β:-0.08, p<0.005) among women. Conclusion MFAP4 levels in plasma were associated with severity of COPD and were correlated to clinical characteristics of the emphysema phenotype.