BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by chronic inflammation and various clinical symptoms, with vitamin D deficiency suggested as a contributing factor. This study aimed to evaluate the effects of vitamin D supplementation on fatigue and disease activity in SLE patients. METHODS: Patients diagnosed based on EULAR/ACR 2019 criteria were divided into three groups: no supplementation, 4000 IU, and 8000 IU of vitamin D daily for six months. Clinical assessments included serum complement levels (C3 and C4), fatigue scores (Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue and Fatigue Severity Scale (FSS)), and disease activity (Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI)). RESULTS: Results showed significant increases in vitamin D levels and serum complement levels in the supplementation groups. Serum complement levels and fatigue scores improved significantly in both the 4000 IU and 8000 IU groups. Additionally, there was a slight reduction in SELENA-SLEDAI scores in the treated groups, but without statistical significance. CONCLUSIONS: The findings suggest that vitamin D supplementation positively affects fatigue and some parameters of disease activity in SLE patients, though its overall impact on disease activity needs further investigation.