Inflammatory bowel diseases are widespread and severe, with Crohn´s disease and ulcerative colitis representing the most prevalent types. It is increasingly recognized that inflammatory processes are always associated with low oxygen tension (hypoxia). Tissue hypoxia requires adaptation of the cells which is mainly controlled by transcription factors designated hypoxia-inducible factors (HIFs), composed of oxygen-regulated α-subunits and a constitutive HIF-1β. Herein, we analyzed how the activation of HIF-1α or HIF-2α subunits in dendritic cells influences the progression of an acute colitis. To this aim, mice with a conditional knockout of HIF-1α or HIF-2α in CD11c expressing cells (dendritic cells) were treated with dextran sodium sulfate to induce experimental colitis. Disease severity was detected by general outcome, weight loss, and measurement of colon weight and length. We determined the severity of inflammation in colon sections from control and knockout mice using immunohistological analysis. Expression of hypoxia-inducible genes in the inflamed colon was studied at the mRNA level. First results show that mice lacking HIF-1α or HIF-2α in dendritic cells lose more weight than controls. Colon samples of these animals showed higher thickness of the tunica submucosa, higher amounts of goblet cells, decreased expression of epithelial cell specific genes, and increased expression of inflammatory genes. We conclude that loss of hypoxia-inducible factors in dendritic cells affects the integrity of the colonic epithelium and may lead to augmented inflammation in an experimental model of acute colitis.