Latar Belakang: Ada asumsi bahwa sindrom kelelahan kronis atau chronic fatigue syndrome (CFS) dikaitkan dengan defisiensi vitamin D. Tujuan: Mencari landasan ilmiah berbasis bukti untuk edukasi serta rekomendasi suplementasi vitamin D untuk memperbaiki kondisi CFS. Metode: Penelusuran database PubMed, Cochrane, OVID, dan Science Direct untuk mencari dan menyaring studi randomized controlled trial (RCT) atau studi longitudinal. Artikel sesuai kriteria inklusi dan eksklusi akan dianalisis lebih lanjut. Hasil: Dari 675 artikel yang disaring, didapatkan 2 studi RCT dan 1 case-control study untuk analisis akhir. Studi RCT Wepner, etal, mendapatkan vitamin D3 2.400 IU/minggu atau 1.200 IU tidak mengurangi rasa nyeri pasien CFS. Studi RCT Witham, et al, menyimpulkan bahwa suplementasi vitamin D3 100.000 IU setiap 2 bulan selama 6 bulan tidak signifikan memperbaiki petanda fungsi vaskular ataupun perbaikan kelelahan pada partisipan CFS (95% CI 0,8 - 1,2; p=0,73). Sedangkan studi case-control Aldaoseri, et al, menunjukkan bahwa kombinasi suplementasi vitamin D dengan antidepresan pada minggu ke-4, 8, dan 12 memperbaiki kelelahan secara signifikan. Simpulan: Dua studi intervensi kualitas sedang dari Witham, dkk. dan Wepner, dkk. menyimpulkan suplementasi vitamin D tidak memiliki pengaruh signifikan terhadap CFS, yang mungkin disebabkan bias karena kadar serum 25 OHD yang cukup bervariasi. Satu studi observasional kualitas sedang menyimpulkan bahwa suplementasi vitamin D memperbaiki kelelahan pada kelompok CFS dengan defisiensi vitamin D. Pemberian vitamin D pada kondisi CFS masih kontroversial dan dapat dipertimbangkan jika ada defisiensi vitamin D. Dibutuhkan studi klinis lanjutan dengan power yang cukup. Background: There is assumption that prevalence of CFS is associated with vitamin D deficiency. We search evidence-based data of vitamin D use for improving CFS. Method: PubMed, Cochrane, OVID, dan Science Direct database was screened, included only randomized controlled trial (RCT) or longitudinal studies. Only qualified studies according our inclusion and exclusion criteria are assessed. Result: From 675 articles screened, 2 RCT and 1 case-control study were included for final analysis. RCT study by Wepner, et al, found no correlation of vitamin D3 2.400 IU/week or 1.200 IU treatment with pain intensity in CFS; RCT study by Witham, et al, concluded that vitamin D3 100,000 IU given every 2 months for 6 months had no significant effect on improving vascular function markers or improvingfatigue symptoms in CFS participants (95% CI 0.8 - 1.2; p=0.73). This finding is in contrast to the case-control study by Aldaoseri, et al, who found that vitamin D supplementation combined with antidepressants at 4, 8, and 12 weeks significantly improved fatigue. Conclusion: Two intervention studies with moderate quality from Witham, et al, and Wepner, et al, concluded that vitamin D supplementation did not have a significant effect on CFS; this result can be confounded by bias due variations of 25 OHD levels. A moderate quality observational study concluded that vitamin D supplementation improved fatigue in the CFS group with vitaminD deficiency. Administration vitamin D supplementation is still controversial and should be considered in certain conditions such as CFS patients with vitamin D deficiency. Future clinical trials with sufficient power are needed.