Abstract Objectives: Telemedicine is gaining ground in the treatment of patients with chronic obstructive pulmonary disease (COPD). Because telemedicine often requires both participation and engagement of the patients, it is important to take differences in cognitive ability into account, as there is evidence that cognitive dysfunction may be a limitation in patients with severe COPD. The aim of this study was to investigate whether cognitive performance is better after telemedicine-based treatment than after conventional hospitalization in patients with severe COPD and a mild to moderate exacerbation. Materials and Methods: This randomized study was a substudy of the "Virtual Hospital," a multicenter, randomized controlled trial. The primary outcome in this substudy was cognitive function, evaluated 3 days and 6 weeks after discharge using a neuropsychological test battery comprising four tests and seven variables. Results: We included 44 patients consecutively. Baseline characteristics were as follows: mean age, 70 (standard deviation [SD] 10) years; mean forced expiratory volume in 1 s, 1.0 (SD 0.55) L (42% of predicted); mean hemoglobin oxygen saturation, 95 (SD 2.0) percent; and mean Mini Mental State Examination score, 27.5 (SD 1.6) points. The performance in all seven neuropsychological test variables tended to be better in the group allocated to virtual admission 3 days and 6 weeks after discharge, but the difference was not significant after Bonferroni's correction for multiple comparisons. Conclusions: There were no significant differences in cognitive performance between the telemedicine-based group and the conventional hospital group. Patients with severe COPD suffering from mild to moderate exacerbations were able to manage the telemedicine-based treatment despite the reduced cognitive function often seen in COPD patients.