Purpose <p>Vitamin D (Vit D) deficiency has been associated with both obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) as well as with their combination, known as overlap syndrome (OS). There is evidence that continuous positive airway pressure (CPAP) may lead to an increase of Vit D levels in OSA patients. However, the effect of CPAP treatment on Vit D levels in OS patients has yet to be determined. The aim of the present study was to investigate the effect of one year of CPAP therapy on Vit D levels in patients with OS.</p> Methods <p>Vit D serum levels were measured in consecutive OS patients at baseline and after one year of CPAP therapy. Compliance with CPAP therapy was assessed by the data retrieved from the CPAP device.</p> Results <p>Vit D serum levels were measured in 46 OS patients (43 males). Among participants, 27 had good and 19 poor compliance with CPAP therapy. Results showed that serum Vit D levels increased after 12 months of CPAP therapy from 21.3 ± 8.4 to 23.8 ± 8.7 ng/ml (<i>p</i> = 0.001). Moreover, patients with good CPAP compliance demonstrated higher serum 25(OH)D levels compared to those with poor compliance (25.8 ± 7.6 versus 20.4 ± 9.6 ng/ml, respectively; <i>p</i> = 0.038).</p> Conclusions <p>In conclusion, 12 months of CPAP therapy improved Vit D serum levels in OS patients, more so in compliant patients.</p>