COPD patients have increased systemic inflammation and increased structural brain damage. 23 COPD patients with coronary artery disease (CAD), and 24 people without COPD matched for smoking, and CAD severity (Gensini score) were studied. COPD patients had more white matter lesions and microstructural tract abnormalities compared to controls. Systemic inflammation (high sensitivity C-reactive protein and fibrinogen) was associated with microstructural brain damage in whole-group analyses. These results suggest a systemic inflammatory process in COPD, which may contribute to white matter abnormalities, consistent with those reported in small vessel disease.