Health advocacy is crucial for both patients and healthcare professionals. However, nurses who recognize the importance of health advocacy may experience heightened moral distress, particularly in complex donation and transplantation cases where patient autonomy, respect, and advocacy are paramount. To identify the factors contributing to moral distress among nurses working in solid organ transplant units at a university hospital in São Paulo, with a focus on health advocacy. This descriptive, cross-sectional study employs both quantitative and qualitative methods. For this, the quantitative phase of the study was conducted utilizing the Moral Distress Scale, while the qualitative phase was executed through focus group discussions. The quantitative phase involved 15 nurses using the Moral Distress Scale. The qualitative phase consisted of a focus group with 5 nurse managers/coordinators from the transplant units. Quantitative data were analyzed using R® software, while qualitative data were analyzed using Bardin's Content Analysis. The study was approved by the Research Ethics Committee of the Ribeirão Preto College of Nursing, University of São Paulo. Participation was voluntary and confidentiality was ensured. A significant correlation was found between moral distress and the factors of "disregard for patient autonomy" (p = .0100) and "therapeutic obstinacy" (p = .0492). The primary determinants associated with moral distress in the context of health advocacy were identified as "disregard for patient autonomy" and "therapeutic obstinacy."