Influenza antivirals are important tools in our fight against annual influenza epidemics and future influenza pandemics. Combinations of antivirals may reduce the likelihood of drug resistance and improve clinical outcomes. Recently, two hospitalised immunocompromised influenza patients, who received a combination of a neuraminidase inhibitor and baloxavir, shed influenza viruses resistant to both drugs. The replicative fitness of one of these A(H1N1)pdm09 virus isolates with dual resistance mutations (NA-H275Y and PA-I38T) was similar to wild type (WT) virus in vitro, but reduced in the upper respiratory tracts of challenged ferrets. In a ferret aerosol transmission model the dual-mutant virus transmitted well between ferrets, but was outcompeted by the WT virus when the two viruses were co-administered. These results indicate that the dual-mutant virus had a moderate loss of viral fitness compared to the WT, suggesting that person-to-person transmission of the dual-resistant virus may be possible, but widespread community transmission is unlikely.