Background: A sequential change in body position from supine-to-both lateral positions under constant ventilatory settings could be used as a postural recruitment maneuver in case of acute respiratory distress syndrome (ARDS), provided that sufficient positive end-expiratory pressure (PEEP) prevents derecruitment. This study aims to evaluate the feasibility and physiological effects of a sequential postural recruitment maneuver in early mechanically ventilated COVID-19 ARDS patients. Methods: A cohort of 15 patients receiving lung-protective mechanical ventilation in volume-controlled with PEEP based on recruitability were prospectively enrolled and evaluated in five sequentially applied positions for 30 min each: Supine-baseline; Lateral-1st side; 2nd Supine; Lateral-2nd side; Supine-final. PEEP level was selected using the recruitment-to-inflation ratio (R/I ratio) based on which patients received PEEP 12 cmH2O for R/I ratio ≤ 0.5 or PEEP 15 cmH2O for R/I ratio > 0.5. At the end of each period, we measured respiratory mechanics, arterial blood gases, lung ultrasound aeration, end-expiratory lung impedance (EELI), and regional distribution of ventilation and perfusion using electric impedance tomography (EIT). Results: Comparing supine baseline and final, respiratory compliance (29 ± 9 vs 32 ± 8 mL/cmH2O; p < 0.01) and PaO2/FIO2 ratio (138 ± 36 vs 164 ± 46 mmHg; p < 0.01) increased, while driving pressure (13 ± 2 vs 11 ± 2 cmH2O; p < 0.01) and lung ultrasound consolidation score decreased [5 (4–5) vs 2 (1–4); p < 0.01]. EELI decreased ventrally (218 ± 205 mL; p < 0.01) and increased dorsally (192 ± 475 mL; p = 0.02), while regional compliance increased in both ventral (11.5 ± 0.7 vs 12.9 ± 0.8 mL/cmH2O; p < 0.01) and dorsal regions (17.1 ± 1.8 vs 18.8 ± 1.8 mL/cmH2O; p < 0.01). Dorsal distribution of perfusion increased (64.8 ± 7.3% vs 66.3 ± 7.2%; p = 0.01). Conclusions: Without increasing airway pressure, a sequential postural recruitment maneuver improves global and regional respiratory mechanics and gas exchange along with a redistribution of EELI from ventral to dorsal lung areas and less consolidation. Trial registration ClinicalTrials.gov, NCT04475068. Registered 17 July 2020, https://clinicaltrials.gov/ct2/show/NCT04475068.