PURPOSE: The purpose of this study was to determine the mediating effects of self-efficacy and the belief about medication on the association between depression and medication adherence in patients with systemic lupus erythematosus. METHODS: 128 patients aged ≥19 years, who were regular outpatients or admitted patients diagnosed with systemic lupus erythematosus at a tertiary hospital in B city, participated in this study. Data were collected by using a self-administered questionnaire. Testing of mediating effects was analyzed by a parallel redundant mediated model using the PROCESS macro for SPSS version 3.3. RESULTS: They scored an average of 16.71±11.13 for depression, 694.14±170.68 for self-efficacy, 3.05±4.60 for the belief about medication, and 90.14±15.37 for medication adherence. The direct effect of depression on medication adherence was not statistically significant, but the indirect effects of depression mediated with self-efficacy and belief about medication were statistically significant. CONCLUSION: It is necessary to develop and apply a nursing intervention program that can not only relieve depression but also promote self-efficacy and the belief about medication with the objective of improving medication adherence among patients with systemic lupus erythematosus.