Purpose This is a physiological study to determine the effect of continuous positive airway pressure and inspiratory support pressure on respiratory effort measured by diaphragm thickening fraction (DTF) during non-invasive respiratory support in healthy volunteers. Materials and Methods DTF was measured in spontaneously breathing, healthy volunteers during 4 phases: (I) Without connection to a ventilator, (II) on a ventilator without any applied pressures, (III) with continuous positive airway pressure of 5 cmH2O and (IV) with additional inspiratory support pressure of 5 cmH2O. Results 29 individuals agreed to participate. DTF was similar during the first two phases (32 ± 13% and 35 ± 22%). A considerable increase in DTF to 51 ± 21% was noted in phase III. The introduction of inspiratory support pressure during phase IV led to a reduction in DTF back to 36 ± 23% (p < 0.001). Tidal volume and minute ventilation were both slightly higher in phase IV compared to phase III. Conclusion Continuous positive airway pressure without inspiratory support pressure increases respiratory effort measured by DTF in healthy subjects. Further research is required to investigate this phenomenon in patients with acute respiratory failure.