Abstract: nutrients Article Vitamin D Supplementation and Clinical Outcomes in Severe COVID-19 Patients—Randomized Controlled Trial Josipa Domazet Bugarin 1 , Svjetlana Dosenovic 1 , Darko Ilic 1 , Nikola Delic 1 , Ivana Saric 1 , Ivo Ugrina 2 , Sanda Stojanovic Stipic 1 , Bozidar Duplancic 1 and Lenko Saric 1, * 1 2 * Citation: Domazet Bugarin, J.; Department of Anesthesiology, Reanimatology and Intensive Care, University Hospital Split, 21000 Split, Croatia Intellomics Ltd., 21000 Split, Croatia Correspondence: lenko.saric@gmail.com Abstract: COVID-19 symptoms vary from asymptomatic cases to moderate and severe illness with patients needing hospitalization and intensive care treatment. Vitamin D is associated with severity of viral infections and has an immune-modulatory effect in immune response. Observational studies showed a negative association of low vitamin D levels and COVID-19 severity and mortality outcomes. In this study, we aimed to determine whether daily supplementation of vitamin D during intensive care unit (ICU) stay in COVID-19 patients with severe illness affects clinically relevant outcomes. Patients with COVID-19 disease in need of respiratory support admitted to the ICU were eligible for inclusion. Patients with low vitamin D levels were randomized into one of two groups: the intervention group received daily supplementation of vitamin D and the control group did not receive vitamin D supplementation. In total, 155 patients were randomized: 78 into the intervention group and 77 into the control group. There was no statistically significant difference in number of days spent on respiratory support, although the trial was underpowered for the main outcome. There was no difference in any of the secondary outcomes analyzed between two groups. Our study suggests no benefit in vitamin D supplementation to patients with severe COVID-19 disease admitted to the ICU and in need of respiratory support in any of the analyzed outcomes. Dosenovic, S.; Ilic, D.; Delic, N.; Saric, I.; Ugrina, I.; Stojanovic Stipic, S.; Keywords: vitamin D; ICU; COVID-19; respiratory support; mechanical ventilation; ARDS Duplancic, B.; Saric, L. Vitamin D Supplementation and Clinical Outcomes in Severe COVID-19 Patients—Randomized Controlled