Chronic obstructive pulmonary disease, as one of the most common lung diseases, has a progressive and debilitating nature and affects patients' psychological performance. It is often accompanied by decline in cognitive abilities. The purpose of this study was to investigate the mediating role of ego depletion in the relationship between negative meta-emotion and fatigue with cognitive failure in patients with chronic obstructive pulmonary disease. For this purpose, in a descriptive-correlational study, 204 patients with chronic obstructive pulmonary disease in Kerman were selected by convenience sampling and were evaluated for cognitive failure, ego depletion, negative meta-emotion, and fatigue. The results of data analysis showed that negative meta-emotion, fatigue and ego depletion have significant positive relationship with cognitive failure. Also, the results of path analysis also suggested that ego depletion plays a partial mediating role in the relationship between negative meta-emotion and fatigue with cognitive failure. That is, part of the relationship between negative meta-emotion and fatigue with cognitive failure occurs through ego depletion. It means, part of the relationship between negative meta-emotion and fatigue with cognitive failure occurs through ego depletion. Therefore, according to the results of the present study, we can reduce the ego depletion in patients with chronic obstructive pulmonary disease by providing therapeutic interventions based on reduction in negative meta-emotion and fatigue, thus preventing or controlling cognitive failure in these patients.