Abstract<p>The negative outcomes of COVID‐19 diseases respiratory distress (ARDS) and the damage to other organs are secondary to a “cytokine storm” and to the attendant oxidative stress. Active hydroxyl‐forms of vitamin D are anti‐inflammatory, induce anti‐oxidative responses, and stimulate innate immunity against infectious agents. These properties are shared by calcitriol and the CYP11A1‐generated non‐calcemic hydroxyderivatives. They inhibit the production of pro‐inflammatory cytokines, downregulate NF‐κΒ, show inverse agonism on RORγ and counteract oxidative stress through the activation of NRF‐2. Therefore, a direct delivery of hydroxyderivatives of vitamin D deserves consideration in the treatment of COVID‐19 or ARDS of different etiology. We also recommend treatment of COVID‐19 patients with high dose vitamin D since populations most vulnerable to this disease are likely vitamin D deficient and patients are already under supervision in the clinics. We hypothesize that different routes of delivery (oral and parenteral) will have different impact on the final outcome.