Purpose <p>Consultations related to major depression have increased significantly in recent years in Primary Care (PC) in Catalonia. PC is key in the approach, so we analysed the training and alignment with clinical practice guidelines (CPGs) of PC professionals in Catalonia and explored their perceptions of the results obtained.</p> Methods <p>Explanatory sequential study. Cross-sectional observational study through surveys carried out on nursing and medical professionals and community emotional wellness referents (RBEC), followed by a qualitative study of phenomenological design through focus groups in the same disciplines.</p> Results <p>Most professionals feel poorly trained (63.5%) and do not consider themselves aligned (58.3%) with the CPGs. In the focus groups, there was a widespread awareness of the PC approach to depression. It was detected that the lack of homogeneity in clinical practice is due to a lack of both time and resources, and a predominantly pharmacological approach. It was expressed that practical training focused on PC, together with collaborative care, unification of CPGs and working with the social determinants of health could help in harmonisation. Moreover, a certain reluctance towards eHealth in the approach to depression was detected.</p> Conclusions <p>It has been detected that professionals feel poorly trained and aligned with CPGs. These results underscore specific aspects like training, the practicality of guidelines, and interdisciplinary collaboration, that warrant further investigation to enhance the treatment of depression within the Catalan healthcare system.</p>