We conducted a cost-utility analysis of a telehealth programme for patients with severe chronic obstructive pulmonary disease (COPD) compared with usual care. A randomized controlled trial was carried out over four months with 45 patients treated with long-term oxygen therapy, 24 in the telehealth group (TG) and 21 in the control group (CG). The analysis took into account whether the severity of comorbidity (defined as the presence of additional chronic diseases co-occurring with COPD) was associated with differences in costs and/or quality-adjusted life years (QALYs). Results of cost-utility analysis were expressed in terms of the incremental cost-effectiveness ratio (ICER). The average total cost was €2300 for the TG and €1103 for the CG, and the average QALY gain was 0.0059 for the TG and 0.0006 for the CG (resulting an ICER of 223,726 €/QALY). For patients without comorbidity, the average total cost was €855 for the TG and €1354 for the CG, and the average QALY gain was 0.0288 for the TG and 0.0082 for the CG (resulting in the telehealth programme being the dominant strategy). For patients with comorbidity, the average total cost was €2782 for the TG and €949 for the CG, and the average QALY gain was -0.0017 for the TG and -0.0041 for the CG (resulting an ICER of 754,592 €/QALY). The telehealth programme may not have been cost-effective compared to usual care, although it could be considered cost-effective for patients without comorbidity.