Tehran University of Medical Sciences Archives of Anesthesiology and Critical Care 2423-5849 0 0 2026 08 01 1680 1680 Khashayar Shahverdi Department of Anesthesiology and Critical Care, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. Fatemeh Afra Department of Clinical Pharmacy, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran. Leila Sadat Hosseini Department of Anesthesiology and Critical Care, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran. Amirmahdi Mojtahedzadeh Faculty of Medicine, Semmelweis University, Budapest, Hungary. Atabak Najafi Department of Anesthesiology and Critical Care, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran. Mojtaba Mojtahedzadeh Division of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. & Division of Critical Care Medicine, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran. 2026 07 02 2026 07 03 Background: Sepsis is a life-threatening condition that frequently leads to intensive care unit (ICU) admission and is characterized by organ dysfunction, high morbidity, and mortality. Severe cases may progress to septic shock, further increasing the risk of death. Vitamin D, especially in its active form, plays a critical role in modulating the immune response. Vitamin D deficiency is common in patients with sepsis and has been associated with worse outcomes. Despite emerging evidence suggesting that supplementation may improve clinical outcomes, results are inconsistent due to variability in study design, patient populations, dosing regimens, and outcome measures. Methods: This protocol outlines a systematic review with potential meta-analysis if sufficient data are available. Randomized-controlled trials (RCTs) evaluating vitamin D supplementation in adult patients with sepsis or septic shock will be included. Primary outcomes will focus on all-cause mortality, while secondary outcomes will include ICU and hospital length of stay, duration of mechanical ventilation, change in sequential organ failure assessment (SOFA) score, and vasopressor requirements. A comprehensive literature search will be conducted in PubMed, Scopus, Embase, and Web of Science, with supplementary searches in grey literature and reference lists. Screening, data extraction, and quality assessment will be conducted independently by multiple researchers using predefined forms and the Cochrane Risk of Bias 2 (RoB2) tool. Data synthesis will include narrative summaries and meta-analysis when appropriate, using standardized statistical methods. Results: This review will systematically synthesize the available evidence regarding the effectiveness of vitamin D supplementation in critically ill patients with sepsis and septic shock. If sufficient homogeneous data are available, a meta-analysis will be performed to generate pooled estimates for mortality and other clinically relevant outcomes. Conclusion: This systematic review and meta-analysis will provide a comprehensive and up-to-date synthesis of evidence regarding vitamin D supplementation in sepsis and septic shock. The findings are expected to clarify the current evidence, identify knowledge gaps, and inform future clinical research and evidence-based practice. https://aacc.tums.ac.ir/index.php/aacc/article/view/1680