Systemic Lupus Erythematosus (SLE) is an immune-mediated disease with severe morbidity and tissue damage. Adherence to therapy in SLE patients remains a significant problem, and nonadherence can lead to poor disease outcomes and decreased quality of life. Self-efficacy is also a critical aspect of disease control and medication adherence. This study aims to evaluate medication adherence, quality of life, and self-efficacy among patients with SLE and their correlation with sociodemographic and clinical factors. This was cross-sectional study was conducted at Baghdad Teaching Hospital's Rheumatology Unit from November 2024 to January 2025, evaluating adherence, quality of life, and self-efficacy among SLE patients using the Compliance Questionnaire for Rheumatology (CQR), the World Health Organisation Quality of Life Questionnaire (WHOQOL-BREF), and Self-Efficacy for Managing Chronic Disease 6-Item Scale (SEMCD) respectively. In addition, the SLEDAI was used to measure the disease activity. The study recruited 118 individuals aged 35.03±10.52 years old on average, and 94.1% did not receive the flu vaccine in the past year. The average CQR score was 64.32, and 12.7% of the patients adhered to the therapy; the WHOQOL-BREF psychological score was at its minimum value of 9.90, while the social score attained the maximum value of 12.21, and the average SEMCD score for the subjects was 39.88. The adherence score significantly correlated with residency and SELENA-SLEDAI. In addition, WHOQOL-BREF scores demonstrated a significant correlation with residency, exercise, SELENA-SLEDAI, disease duration, and the number of chronic diseases. The SES6C score is also associated with residency, SELENA-SLEDAI, and the number of chronic drugs. The study identified a significant positive correlation among self-efficacy scores, medication adherence scores, and four aspects of quality of life. The study concluded that patients with SLE demonstrated low flu vaccine uptake, suboptimal medication adherence, relatively low quality of life regarding the psychological domain score, and relatively high self-efficacy in managing chronic disease. Finally, the study revealed the need for effective communication between healthcare providers and patients regarding infection risks and benefits of flu vaccine. Furthermore, augmenting patient education to enhance medication adherence and improve self-efficacy in managing chronic disease can positively impact treatment outcomes and, hence, patient quality of life.