Background: Chronic obstructive pulmonary disease (COPD) is a well-recognized multicomponent disease, but its influences on cognitive function and other associated psychological disorders were poorly identified. Systemic inflammation is considered as a key link between these diseases. Aim: To assess the cognitive impairment, anxiety, and depression among stable COPD patients using different neuropsychological tests, in relation with serum interleukin- 6 (IL-6). Patients and methods: A study was conducted upon 100 stable COPD patients and 25 controls. All the participants were subjected to neurological and psychiatric assessment, such as The Generalized Anxiety Disorder-7 scale, Beck Depression Inventory-II scale, and Montreal Cognitive Assessment scale. Serum IL-6 was measured for all participants. Results: COPD patients had more frequent anxiety disorders, depression, cognitive dysfunction, and higher serum IL-6 than control group. Visual-spatial/executive and delayed recall domains of cognitive dysfunction were significantly affected in COPD than controls (P<0.001), whereas other domains (Naming, Attention, Language, Abstraction, and Orientation) did not reach a significant level of statistical difference. Generalized Anxiety Disorder-7 anxiety score showed a significant positive correlation with modified medical research council and serum IL-6 and a significant negative correlation with forced expiratory volume in the first second%. Beck Depression Inventory-II score showed a significant positive correlation with BMI. Montreal Cognitive Assessment score showed a significant positive correlation with forced expiratory volume in the first second% and a significant negative correlation with serum IL-6. A cut-off value of serum IL-6 more than 2.6 pg/ml had sensitivity and specificity for prediction of cognitive dysfunction in COPD patients (86.1 and 66.7%, respectively; P<0.001). Conclusion: Anxiety, depression, and cognitive impairment were significantly more prevalent between COPD patients. Serum IL-6 was a valid predictor for cognitive dysfunction in COPD patients.