Impaired cognitive function is increasingly recognized in COPD. Yet, the prevalence of cognitive impairment in specific cognitive domains in COPD has been poorly studied. The aim of this cross-sectional observational study was to compare the prevalence of domain-specific cognitive impairment between patients with COPD and non-COPD controls. A neuropsychological assessment was administered in 90 stable COPD patients and 90 non-COPD controls with comparable smoking status, age, and level of education. Six core tests from the Maastricht Aging Study were used to assess general cognitive impairment. By using Z-scores, compound scores were constructed for the following domains: psychomotor speed, planning, working memory, verbal memory, and cognitive flexibility. General cognitive impairment and domain-specific cognitive impairment were compared between COPD patients and controls after correction for comorbidities using multivariate linear and logistic regression models. General cognitive impairment was found in 56.7% of patients with COPD and in 13.3% of controls. Deficits in the following domains were more often present in patients with COPD after correction for comorbidities: psychomotor speed (17.8% vs 3.3%; P,0.001), planning (17.8% vs 1.1%; P,0.001), and cognitive flexibility (43.3% vs 12.2%; P,0.001). General cognitive impairment and impairments in the domains psychomotor speed, planning, and cognitive flexibility affect the COPD patients more than their matched controls.