The origin(s) of systemic inflammation in patients with chronic obstructive pulmonary disease (COPD) is unclear. We investigated the impact of exposure to ambient air pollution on systemic biomarkers of inflammation (C-reactive protein (CRP), tumour necrosis factor-α, interleukin (IL)-6, IL-8 and fibrinogen) and tissue repair (hepatocyte growth factor (HGF)) in 242 clinically stable COPD patients (mean age 67.8 years and forced expiratory volume in 1 s 71.3% predicted) in Barcelona, Spain, in 2004-2006. A spatiotemporal exposure assessment framework was applied to predict ambient nitrogen dioxide (NO <inf>2</inf>) and levels of particles with a 50% cut-off aerodynamic diameter of 2.5 μm (PM2.5) at each participant's home address during 10 periods of 24 h (lags 1-10) and 1 year prior to the blood sampling date. We used linear regression models to estimate associations between biomarkers and exposure levels. An interquartile range (IQR) increase in NO<inf>2</inf> exposure in lag 5 was associated with 51%, 10% and 9% increases in CRP, fibrinogen and HGF levels respectively. We also observed 12% and 8% increases in IL-8 associated with an IQR increase in NO<inf>2</inf> exposure in lag 3 and over the year before sampling, respectively. These increases were larger in former smokers. The results for PM2.5 were not conclusive. These results show that exposure to ambient NO<inf>2</inf> increases systemic inflammation in COPD patients, especially in former smokers. Copyright © ERS 2014.