Vitamin D is involved in immune regulation in humans. Vitamin D serum deficiency is reported to be common in hospitalized patients, especially among Intensive Care Unit (ICU) patients. Our aim was to evaluate the relationship between vitamin D levels in septic patients and outcome. A total of 170 patients were studied, of which 92 were severe sepsis/septic shock patients, and 72 were major trauma patients, as an age-matched control group. Exclusion criteria were: age <18 years (y), malnutrition state, pregnancy, breast feeding, chemotherapy, immunotherapy, pathologies affecting bone and calcium metabolism, vitamin D metabolism derangement for therapy, hematological and solid malignancies, and HIV. Vitamin D levels were measured by radioimmunoassay at admission. Median vitamin D levels at admission to ICU were 10.1 ng/mL in the sepsis group and 18.4 ng/mL in the trauma group (P<0.0001). In univariate analysis, mortality rate in septic patients was significantly correlated with age, gender, SAPS II, vitamin D level at admission, duration of mechanical ventilation, and ICU/hospital length of stay, however, the multivariate logistic regression model confirmed significance only for age. In our cohort, septic patients showed a significantly lower vitamin D level than trauma patients in comparison to age cohort patients with the same demographic/clinical characteristics, but no clear relationship between vitamin D level and outcome was found. Further studies with larger samples are needed to clarify the prognostic role of vitamin D and nutraceutical interventions in critically ill patients.