Using alternative feed ingredients in pig diets can lead to deoxynivalenol (DON) contamination. DON has been shown to induce anorexia, inflammation, and—more recently—alterations in the vitamin D, calcium, and phosphorus metabolisms. Adding vitamin D supplementation in the form of vitamin D3and 25-OH-D3to the feed could modify the effects of DON in piglets. In this study, vitamin D3or 25-OH-D3supplementation was used in a control or DON-contaminated treatment. A repetitive exposure over 21 days to DON in the piglets led to disruptions in the vitamin D, calcium, and phosphorus metabolisms, resulting in a decreased growth performance, increased bone mineralization, and the downregulation of genes related to calcium and to phosphorus intestinal and renal absorption. The DON challenge also decreased blood concentrations of 25-OH-D3, 1,25-(OH)2-D3, and phosphate. The DON contamination likely decreased the piglets’ vitamin D status indirectly by modifying the calcium metabolism response. Vitamin D supplementations did not restore vitamin D status or bone mineralization. After a lipopolysaccharide-induced inflammatory stimulation, feeding a 25-OH-D3supplementation increased 25-OH-D3concentration and 1,25-(OH)2-D3regulations during the DON challenge. DON contamination likely induced a Ca afflux by altering the intestinal barrier, which resulted in hypercalcemia and hypovitaminosis D. The vitamin D supplementation could increase the calcitriol production to face the combined LPS and DON challenge.