This study aims to assess the role of vitamin D on systemic lupus erythematosus (SLE) patients and its effects on systemic lupus erythematosus disease activity index (SLEDAI), anti-double-stranded DNA (anti-dsDNA), C3, C4, and fatigue in patients with SLE. A systemic search was conducted using three electronic databases, i.e., PubMed/Medline, Cochrane Library, and Google Scholar. Review Manager 5.4.1 (The Cochrane Collaboration, The Nordic Cochrane Centre, Copenhagen, Denmark) was employed for statistical analysis. All studies meeting the inclusion criteria were selected. A random-effect model was used to pool the studies, and the result was reported in the standard mean difference (SMD) with its corresponding 95% confidence interval. Six randomized controlled trials were selected. Five outcomes were assessed (SLEDAI, anti-dsDNA, C3, C4, and fatigue) to evaluate the role of vitamin D in SLE patients. A significant decrease in SLEDAI (SMD = -0.85 (-1.12, -0.58); p < 0.00001; I 2 = 42%) and a non-significant decrease in anti-dsDNA (SMD = -0.09 (-0.03, 0.12); p = 0.42; I 2 = 0%) was noted. A significant increase in levels of C3 (SMD = 0.30 (0.09, 0.51); p = 0.006; I 2 = 0%) and fatigue (SMD = -1.27 (-2.38, -0.16); p = 0.02; I 2 = 56%) was noted when vitamin D was used. Insignificant difference was observed in C4 (SMD = 0.20 (-0.02, 0.41); p = 0.07; I 2 = 0%). Vitamin D in SLE patients showed a significant decrease in SLEDAI scores and a significant increase in C3 levels. The effect of vitamin D on fatigue was inconclusive. No significant difference in anti-dsDNA and C4 levels was noted.

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