Background: Pharmaceutical aerosols are typically not administered through a low flow nasal cannula oxygen system due to expected negligible emitted dose (ED). However, advantages of nose-to-lung aerosol delivery through a low flow nasal cannula (LFNC) system include convenient administration of medicines with high doses or long delivery times as well as administration of aerosols to unconscious patients or those not able to effectively use an inhaler. Methods: An in vitro system for effectively generating a dry powder aerosol and delivering the aerosol simultaneously with LFNC therapy was developed. The dry powder inhaler (DPI) was a new inline device containing a 3D rod array structure to aerosolize a model excipient enhanced growth (EEG) formulation using the 5 L/min flow rate of the LFNC system. Commercial (CM) and streamlined (SL) versions of the Y-connector and small bore nasal cannula interface were tested. Results: Based on in vitro experiments with a flow rate of 5 L/min for 60 s, ED increased from 36% with the CM configuration to 61.4% with SL components and 4 mm internal diameter tubing. The streamlining approach had a significant effect on reducing depositional losses in the system components including an order of magnitude reduction in nasal cannula loss alone. Conclusions: The developed device and EEG formulation together can provide high quality aerosol delivery to a patient simultaneously receiving LFNC therapy by simply connecting the inline DPI and replacing the CM connectors with new SL components.