Non-COVID-19 sepsis (Sepsis) has always been one of the common diseases in critically ill patients. The main treatment strategy is to kill pathogens and mitigate hyperinflammation. One study demonstrated that the supplementation with 576,000 IU cholecalciferol (vitamin D3) as a single dose in critically ill adults in the medical intensive care units (MICUs) can improve clinical outcomes, including acute physiology and chronic health evaluation II score (APACHE II), sequential organ failure assessment score (SOFA), and C-reactive protein (CRP).

It is a three-year, multi-center, prospective, parallel, double-blind, randomized controlled clinical trial for 240 eligible subjects, with administrations of vitamin D3 576,000 IU or placebo every 24 hours for 3 days (72 hours) within 96 hours after intensive care unit (ICU) admission.

Inclusion Criteria:

1. Medical subject ≥ 18 years old and diagnosed with sepsis
2. Transferred to the intensive care unit within 24 hours after being diagnosed with sepsis
3. Admitted to the ICU with 40 > APACHE II score ≥ 15.
4. The intensivist anticipates that the subject will stay in the ICU ≥ 7 days.

Exclusion Criteria:

1. Diseases that affect serum levels of 25(OH)D and calcium, including thyroidectomy, parathyroid disease, rickets, or severe cirrhosis [Child C]
2. Received large doses of vitamin D3 in the past four weeks (> 2000 IU per day or ≥ 10,000 IU in a single dose)
3. Admitted to the ICU with diagnosis of COVID-19
4. AIDS subjects taking immunosuppressants
5. Organ transplant
6. Active cancer
7. Tuberculosis, sarcoidosis, or kidney stones in the past one year
8. Weight < 45 kg or > 90 kg
9. Had been admitted to ICU in the past three months
10. Subject and family members who do not speak the native language
11. Pregnant women