Background: Vitamin D deficiency is increased among patients with systemic lupus erythematosus (SLE). The vitamin D is a potent regulator of the immune system and may suppress inflammatory responses. Vitamin D may be a safe helper to reduce systemic inflammation in these patients. The objectives of this study were to assess are vitamin D deficiency, the effect of high dose therapy in SLE patients and its relationship with disease activity. Methods: Data were collected from 120 SLE patients attending out patients clinic Benha faculty of medicine rheumatology department between September 2015 and march 2016, 80 SLE patients with vitamin D therapy as patient group and 40 SLE patients without vitamin D therapy as control group. Serum 25-hydroxyvitamin D concentration and disease activity (SLEDAI) had recorded for both group at baseline and after three months. Patients group received cholecalciferol 50,000 IU once weekly for 3 months. Statistical methods were used to determine the correlation of serum vitamin D level and disease activity both at baseline and at 12 weeks. The 40 control SLE patients didn't receive any vitamin D supplementation during the time of study. The patients and control groups were similar regarding age, body mass index, organ involvement, glucocorticoid dose, use of immunosuppressive drugs. Results: Vitamin D deficiency (