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Objective: To conduct a systematic review of the literature on the impact of spirituality/religiosity (S/R) on the health-disease process of individuals with sickle cell disease (SCD) and acquaint health professionals with the possibility of using complementary and alternative measures (CAM) in association with conventional treatment, especially the use of S/R in SCD. Methods: SciELO, BIREME, Medline, PubMed and Lilacs electronic databases were searched for articles published between 10 and 18 May 2020 that include the descriptors "spirituality", "religion" and "sickle cell disease". Inclusion criteria: articles that established any correlation between S/R and patients with SCD. Exclusion criteria: articles not relevant to the S/R and SCD correlation. Twenty-seven scientific articles were selected. Results: We were able to verify that the use of CAM in the management of patients with SCD is associated with better coping. S/R is a widely used resource and it has shown significant results in the quality of life of this population. Final considerations: The use of S/R is part of the comprehensive care for patients with SCD and should be associated with conventional therapeutic management. Health professionals commonly find difficult to approach and associate S/R with patient treatment. Therefore, training on this matter would be indicated.