Two types of high flow nasal cannula (HFNC) oxygen therapy were tested using computational models of the human upper airway to investigate cannula geometry's effect on CO2 flush. Models were run with a generic HFNC geometry, two High Velocity Nasal Insufflation (HVNI) cannula geometries, and without any cannula, each for open and closed mouth patient scenarios. For the open mouth scenario, models included either an inflamed left nasal passageway or a healthy (uninflamed) left nasal passageway. With a healthy left nasal passageway and open mouth, the CO2 remaining in the airway at end-exhale was 1.88 mg and 1.84 mg for the HVNI cannulas, 2.56 mg for HFNC, and 10.0 mg for the model with no cannula. With an inflamed left nasal passageway and open mouth, the CO2 remaining was 1.97 mg, 1.95 mg, 4.24 mg, and 10.5 mg for the same sequence of therapy types. For the closed mouth models, the distinction between therapy types was negligible. It was found that the higher momentum from the HVNI cannulas created a higher resistance against the infiltration of exhaled CO2 into the upper airway. The HVNI cannulas also began flushing the airway (reducing total CO2 mass) earlier in the exhalation cycle than both the HFNC and no-cannula models. The higher resistance to expiratory flow entering the upper airway and earlier transition to flush led to HVNI therapy having the lowest values of CO2 remaining in the airway.