BACKGROUND: The F-IO2 for a nasal cannula with constant flow (CF) depends on the anatomic reservoir (AR), which is affected by changes in frequency and end-expiratory flow. Conversely, pulse flow (PF) devices do not require the AR. The purpose of this study was to compare the F-IO2 delivered by a nasal cannula supplied by CF via oxygen tank with that delivered by PF delivered via portable oxygen concentrator. Hypotheses were (1) a lung model of COPD with non-zero end-expiratory flow decreases F-IO2 for CF more than for PF, and (2) CF and PF perform differently in terms of F-IO2 delivery, despite having equivalent settings. METHODS: Normal and COPD lung models were simulated (Ing Mar Medical ASL 5000) using published human data: normal: breathing frequency = 15 breaths/min, R-in = 4 cm H2O center dot s center dot L-1, R-out = 4 cm H2O center dot s center dot L-1, C = 60 mL center dot cm H2O-1, tidal volume (V-T) = 685 mL, P-max = 11.95 cm H2O, increase = 33%, and release = 28; COPD: breathing frequency = 20 breaths/min, R-in = 12 cm H2O center dot s center dot L-1, R-out = 25 cm H2O center dot s center dot L-1, C = 66 mL center dot cm H2O-1, V-T = 685 mL, P-max = 24.52 cm H2O, increase = 35%, and release = 23%. CF was 1-5 L/min. Portable oxygen concentrators used were Solo(2) (Invacare), XPO2 (Invacare), FreeStyle (AirSep), Focus (AirSep), One G3 (Inogen), and LifeChoice ActivOx (Inova Labs). RESULTS: CF produced significantly higher F-IO2 at all settings for normal lungs but lower for COPD lungs compared with Solo(2). COPD reduced the F-IO2 for CF but had a smaller variable effect for PF. Data show there is no equivalency between PF setting and CF rates for the portable oxygen concentrators tested. CONCLUSIONS: CF oxygen delivery via a nasal cannula is significantly reduced by elimination of the AR in a model of COPD, yielding clinically important decreases in F-IO2. PF (delivered with a portable oxygen concentrator) is relatively unaffected. This study supports the recommendation that clinicians and caretakers should titrate the PF setting to each patient's unique oxygen requirements.