We have discovered that COVID-19 patients with high plasma interleukin (IL)-13 levels have a significantly greater risk of needing mechanical ventilation. IL-13, which signals through the receptor IL-4Rα along with the closely related cytokine IL-4, is involved in eosinophilic inflammation, mucous secretion, goblet cell metaplasia and fibrosis, and has been regularly implicated in airway hyperresponsiveness and atopic disease. It was therefore plausible that IL-13 could exacerbate respiratory disease in COVID-19. Neutralization of IL-13 in K18-hACE2 C57Bl/6J mice protected the animals from severe infection with SARS-CoV-2, as evidenced by reduced clinical score, weight loss and mortality. RNA-seq analysis of whole lung tissue taken from infected mice who underwent IL-13 neutralization revealed the most downregulated gene to be Has1, which encodes a synthase responsible for hyaluronan (HA) production, a polysaccharide apart of the extracellular matrix that has previously been implicated in other inflammatory pulmonary diseases. This was mechanistically further supported by an increase in HA deposition in human and mouse lung upon SARS-CoV-2 infection. Additionally, neutralization of the HA receptor, CD44, led to improved survival in K18-hACE2 mice. As HA has been proposed previously in asthma as a potential culprit in airway remodeling, we hypothesize that HA, as a downstream effector of IL-13, may be involved in pulmonary dysfunction post recovery from COVID-19.