Abstract Background The use of awake prone position concomitant to non-invasive mechanical ventilation in acute respiratory distress syndrome (ARDS) secondary to COVID-19 has shown to improve gas exchange, whereas its effect on the work of breathing remain unclear. The objective of this study was to evaluate the effects of awake prone position during helmet continuous positive airway pressure (CPAP) ventilation on inspiratory effort, gas exchange and comfort of breathing. Methods Forty consecutive patients presenting with ARDS due to COVID-19 were prospectively enrolled. Gas exchange, esophageal pressure swing (ΔPes), dynamic transpulmonary pressure (dTPP), modified pressure time product (mPTP), work of breathing (WOB) and comfort of breathing, were recorded on supine position and after 3 h on prone position. Results The median applied PEEP with helmet CPAP was 10 [8–10] cmH₂O. The PaO₂/FiO₂ was higher in prone compared to supine position (Supine: 166 [136–224] mmHg, Prone: 314 [232–398] mmHg, p < 0.001). Respiratory rate and minute ventilation decreased from supine to prone position from 20 [17–24] to 17 [15–19] b/min (p < 0.001) and from 8.6 [7.3–10.6] to 7.7 [6.6–8.6] L/min (p < 0.001), respectively. Prone position did not reduce ΔPes (Supine: − 7 [− 9 to − 5] cmH₂O, Prone: − 6 [− 9 to − 5] cmH₂O, p = 0.31) and dTPP (Supine: 17 [14–19] cmH₂O, Prone: 16 [14–18] cmH₂O, p = 0.34). Conversely, mPTP and WOB decreased from 152 [104–197] to 118 [90–150] cmH₂O/min (p < 0.001) and from 146 [120–185] to 114 [95–151] cmH₂O L/min (p < 0.001), respectively. Twenty-six (65%) patients experienced a reduction in WOB of more than 10%. The overall sensation of dyspnea was lower in prone position (p = 0.005). Conclusions Awake prone position with helmet CPAP enables a reduction in the work of breathing and an improvement in oxygenation in COVID-19-associated ARDS.