The mesenchymal conversion of epithelial cells (EMT) has been suggested as a potential contributor in cystic fibrosis (CF) disease progression. Endothelial cells (EndCs), the cells lining blood vessels, express functional CFTR and CFTR impairment promotes endothelial activation and dysfunction. However, if the mesenchymal switch also exists in CF EndCs remains uncharacterized. To understand whether the endothelial-to-mesenchymal transition (EndMT) could occur in CF, we have conducted a transcriptomic meta-analysis of primary CFTR-impaired and patient-derived EndCs, and further compared our results to data from CF epithelial cells (EpCs) where EMT has been demonstrated. As compared to EpCs, we show that CFTR-impaired EndCs display a limited signature of EndMT, and that expression of the mesenchymal inducer Twist1 remained unchanged. Nonetheless, the use of CFTR modulators reduced the expression of mesenchymal markers from CF patient-derived EndCs, suggesting an additional therapeutic added-value next to the known effect on CFTR ion transport.