We describe a case of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) to multiple CFTR modulators and piperacillin in an 8 year old female with CF. To our knowledge this is the first reported case of delayed type, T-cell mediated hypersensitivity to multiple CFTR modulators described in literature. Our findings suggest possible cross-reactivity between CFTR modulators or multiple sensitisations, which should be taken into account in similar cases.