To maintain arterial oxygen saturation (Sa,O2) above 90% in patients with acute respiratory failure, oxygen (O2) is often added to the circuit of two-level noninvasive positive pressure ventilation (NPPV). However, the final inspiratory oxygen fraction (Fi,O2) is not known. To clarify this issue, the effect of different inspiratory positive airway pressures (IPAP) of the oxygen tubing connection site and the flow rate of O2, on Fi,O2 was assessed. The effects of the tidal volume (VT) and the respiratory rate on the Fi,O2 were then clarified in a model study. The Fi,O2 varied depending on the point where O2 was added to the circuit. When all other variables were constant, the connection closest to the exhaust port (ventilator side) gave the highest Fi,O2. Increases in IPAP led to decreases in Fi,O2. Finally, Fi,O2 increased with O2 flow, although it was difficult to obtain an Fi,O2 >0.30 unless very high O2 flows were used. Paradoxically, NPPV with low IPAP values and without O2 supplementation led to a Fi,O2 <0.21 at the circuit-patient interface. VT and respiratory rate did not appear to influence Fi,O2. To conclude, when using noninvasive positive pressure ventilation with two-level respirators, oxygen should be added close to the exhaust port (ventilator side) of the circuit. If inspiratory airway pressure levels are >12 cmH2O, oxygen flows should be at least 4 L x min(-1).