The relationship between respiratory system mechanics, lung ultrasound (LUS) abnormalities, and mortality in mechanically ventilated patients with COVID-19-associated respiratory failure is unknown. We assessed the pattern of respiratory mechanics and LUS, their changes over time, and the differences between survivors and non-survivors. We additionally analyzed the relationship between LUS findings and the severity of gas exchange impairment and interleukin 6 (IL-6). This was a twocenter retrospective, observational trial carried out in the intensive care units of the hospitals of Bolzano and Merano, Italy, from March 15 to April 20, 2020. We enrolled 41 consecutive patients. Seven patients (17%, 95% CI 8.5-31.3%) died. Mean compliance of the respiratory system on ICU admission was 41.6 (± 18.8) ml/mbar (42.5 (± 19.6) for survivors, 38.0 (± 16.3) for deceased, p = 0.605). Non-survivors had a significantly lower compliance over time, decreasing from day 14 after symptom onset, compared with survivors (p = 0.008). Mean LUS score on admission was 11.2 (± 3.7) and survivors had lower LUS scores on admission than non-survivors (10.5 (± 3.6), 13.9 (2.8), respectively, t test, p = 0.029). LUS score correlated with IL-6 concentrations (r = 0.52, p = 0.001) and arterial pCO 2 (r = 0.30, p = 0.033) and was inversely correlated with oxygenation (r = − 0.34, p = 0.001). No correlation was found between LUS and respiratory system compliance (r = − 0.02, p = 0.299). Nonsurvivors from COVID-19-associated respiratory failure had a significant decrease in compliance after day 14 of symptom onset. Compliance did not correlate with the degree of abnormalities found in LUS, but LUS score correlated with oxygenation, pCO 2 , and IL-6. Keywords COVID-19. ARDS. Mechanical ventilation. Lung ultrasound. Respiratory mechanics Background A new form of viral pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in Wuhan, China, in December 2019 [1-3]. Due to its transmission dynamics, the virus spread quickly across the globe within a very short time and on March 11, 2020, the WHO declared the outbreak a pandemic [4]. Studies from Marco Rojatti and Ivo B. Regli contributed equally to this work. This article is part of the Topical Collection on COVID-19