The connection between sickle cell disease and depression, although crucial, remains an inadequately explored field, calling for further investigation. This notably concerning health scenario demands more specialized attention from professionals in the field. The present study aims to meticulously analyze the relationship between sickle cell disease and depression, delving into the state of the art on this subject, incorporating sources such as articles, books, dissertations, and theses. Individuals with sickle cell disease show a propensity for elevated levels of depression compared to the general population. Additionally, it has been observed that patients with sickle cell disease and depression experience an intensification of pain compared to their counterparts without depression, suggesting an intrinsic correlation between pain and both conditions. The in-depth analysis of the pathophysiology of both sickle cell disease and depression played a fundamental role in understanding this interconnection. It is concluded that the quality of life for these individuals is compromised, not only in terms of pathophysiological aspects but also in the realms of mental health, highlighting a significant increase in morbidity associated with the presence of depression. In this context, seeking medical assistance proves crucial to mitigate the impacts on the mental health of individuals with sickle cell disease, emphasizing the need for a holistic and integrated approach to substantially improve their quality of life.