Background & Objectives: Supplemental oxygen and aerosol therapy may be used in combination as a treatment for neonates suffering from hypoxemia caused by respiratory diseases. Due to cost and lack of availability of oxygen cylinders in some countries, oxygen concentrators are a reported substitute. This study was designed to determine whether using an oxygen concentrator and low-flow oxygen therapy impacts aerosol drug delivery in a simulated spontaneously breathing neonate patient. Methods: A vibrating mesh nebuliser (VMN; Aerogen Solo) was used to aerosolise a 500µL dose of salbutamol. The aerosol was delivered via a nasal cannula to a neonate head model in combination with oxygen concentrator at gas flow rates of 0.2, 1.0 and 5.0 LPM and low-flow oxygen therapy at gas flow rates of 1.0, 4.0 and 5.0 LPM. The mass of drug in terms of emitted and tracheal doses were recorded. The impact of VMN operation and refill on circuit pressure in both systems was also measured. Results: The oxygen concentrator delivered a higher emitted dose than the low flow system, the largest emitted dose (%) being 20.58 ± 0.50% and 14.69 ± 0.89% respectively at 1.0 LPM , p = 0.018. The largest tracheal dose (%) was generated with the oxygen concentrator, 11.01 ± 0.29% at 5.0LPM compared to 9.66 ± 1.53% for low-flow oxygen therapy, p = 0.073. Refill and operation of the VMN did not impact the circuit pressure in either system. Conclusions: This study shows that the system used to provide combinational aerosol and supplemental oxygen therapy has a significant impact on the quantity of nebulised therapeutic delivered to the patient.