Background: In patients who are critically unwell, sepsis could be one of major causes of mortality as well as many complications. Sepsis is the medical term describing dysfunctional body reaction to infection that results in dysfunctions in various body systems and hence severe organ failure could occur. A rise of 2 or more points in the sequential organ failure evaluation is an early indicator of organ dysfunction (SOFA score). Severe organ failure can occur if sepsis is left untreated. An infection-controlling effect of vitamin D has been demonstrated. With an increase in cathelicidin antimicrobial peptide (AMP) LL-37, human skin, blood plasma, monocytes, and macrophages are all affected. LL-37 and other AMPs, which operate directly against bacteria, regulate numerous innate and adaptive immunological functions. Objective: To make an overview of role of lack of vitamin D (25(OH) D) as well as AMP, LL-37, as risk factors for sepsis. Conclusion: Severe infections, as well as sepsis, have been linked to a deficiency of vitamin D. However, it is not yet clear what the underlying linkage and its clinical consequence is between sepsis and respiratory tract infections as well as critical illness.