To assess serum 25-hydroxyvitamin D (25-OH vitamin D) status in Saudi children with systemic lupus erythematosus (SLE) and determined its association with clinical, laboratory variables and disease activity. This cross-sectional study comprised children with SLE who are followed at Pediatric Lupus Clinic. All patients reviewed for demographic data, age of first disease manifestations, and disease duration. All included patients evaluated for disease activity, which is completed by using the SLE Disease Activity Index (SLEDAI) and laboratory parameters included a vitamin D profile, bone markers at enrollment and 3 months later. All patients treated with Cholecalciferol (vitamin D3 2000 IU daily) and calcium supplement (Caltrate 600 mg twice daily). Twenty-eight patients (26 female) with mean age of 9.7 years completed the evaluation. Fifteen patients had more than one major organ involvement. Most of the patients are on daily vitamin D3 supplement (800 IU) prior enrollment. The baseline assessment revealed 24 patients had low levels of serum 25-OH vitamin D levels, with a mean of 51.1 ± 33.6 nmol/L; 25 patients had high autoantibodies; and 18 patients had high protein/creatinine ratio, with a mean of 0.9 ± 1.7. Bone density was subnormal with a mean of 0.9 ± 1. The mean disease activity was 6 ± 5.6. Levels of 25-OH vitamin D correlated inversely with autoantibodies and SLEDAI and positively with bone density but not statistically significant. After 3 months, treatment of vitamin D3 (2000 IU daily) and Caltrate (600 mg twice daily), 17 patients had improvement in SLEDAI score and autoimmune markers. Disease activity of childhood SLE is probably linked with low serum 25-OH vitamin D levels. Accordingly, high daily vitamin D3 supplement could potentially impact disease activity of childhood SLE. Further follow up and more patients needed to confirm this finding.