Previous studies have shown that aging can contribute to cognitive decline in patients with COPD, whereas cognitive reserve (CR) can be a protective factor against cognitive decline following brain pathology. However, the effects of CR and the interaction between age and CR on cognitive functions in patients with COPD have not been studied. We investigated the effects of age as a risk factor and CR as a protective factor on information processing speed, visuospatial working memory, and cognitive failures in 104 middle-aged (Mage = 58.75 years, SDage = 3.51) and 104 elderly (Mage = 69.43 years, SDage = 3.12) patients with COPD. In addition, this study aimed to explore the interaction effect of age and CR on information processing speed, visuospatial working memory, and cognitive failures in middle-aged and elderly patients with COPD. The findings of the present study showed that (1) age significantly affects information processing speed, visuospatial working memory, and cognitive failures in patients with COPD. (2) CR has a significant effect on information processing speed and cognitive failures in COPD patients, but we did not observe the effect of CR on visuospatial working memory in COPD patients. It was also found that (3) the interaction effect of age and CR was only observed on cognitive failures, while the interaction of age and CR had no significant effect on information processing speed and visuospatial working memory in COPD patients. This study brings to light the differential effects of age and CR on the cognitive domains in COPD patients.