Background Invasive fungal infection is a major source of morbidity and mortality. The usage of microbial cell-free DNA for the detection and identification of invasive fungal infection has been considered as a potential alternative to invasive procedures allowing for rapid results. Objective This analysis aimed to assess the budget implications of using the Karius® Test in patients suspected of invasive fungal infection in an average state in the USA from a healthcare payer perspective. Methods The analysis used a decision tree to capture key stages of the patient pathway, from suspected invasive fungal infection to either receiving treatment for invasive fungal infection or being confirmed as having no invasive fungal infection. The analysis used published costs and resource use from a targeted review of the literature. Because of the paucity of published evidence on the reduction of diagnostic tests displaced by the Karius Test, the analysis used a 50% reduction in the use of bronchoscopy and/or bronchoalveolar lavage. The impact of this reduction was tested in a scenario analysis. Results The results of the analysis show that the introduction of the Karius Test is associated with a cost saving of US 2277perpatient;whenmultipliedbytheestimatednumberofcasesperyear,thecostsavingisUS 17,039,666. The scenario analysis showed that the Karius Test only had an incremental cost of US 87perpatientwhentherewasnoreductioninbronchoscopyandbronchoalveolarlavage.ConclusionsTheKariusTestmayofferavaluableandtimelyoptionforthediagnosisofinvasivefungalinfectionthroughitsnon-invasiveapproachandsubsequentcostsavings.