Cystic Fibrosis is an autosomal recessive disease affecting 1:3000 people in Australasia. It is caused by a mutation in the CFTR gene which causes dehydrated and sticky mucous in the lungs which inhibits mucociliary clearance. Viruses such as rhinovirus, causing the common cold, can present as a more serious illness in people with cystic fibrosis. However, it is still unclear whether this is directly due to the CFTR mutation, or if this is because of long-term stress and damage of the lungs. To explore this, we used human induced pluripotent stem cells (hiPSCs) harbouring the most common CFTR mutation (ΔF508) alongside an isogenic control. These iPSCs were differentiated into airway basal cells, then were plated at an Air-Liquid Interface to mature into a pseudostratified airway epithelium, before being infected with rhinovirus. At several timepoints post-infection, cell death was measured, barrier integrity was assessed using Transepithelial Electrical Resistance (TEER), and RNA collected to measure gene expression. Rhinovirus infection triggered significantly more cell death in ΔF508 airway epithelial cells compared to isogenic controls. Antiviral cytokines, such as IL28A and IFNB1, were upregulated early in infection, although this was significantly impaired in the ΔF508 airway epithelial cells. We saw a similar expression pattern for interferon stimulated genes and proinflammatory cytokines. Rhinovirus infection significantly disrupted TEER regardless of genotype. Our findings suggest that the CFTR ΔF508 mutation causes intrinsic differences in rhinovirus infection response. In future studies we will explore additional CFTR mutations (e.g., W1282X) and respiratory pathogens, and whether CFTR modulators can restore infection responses in ΔF508 airway epithelium.