BackgroundMechanisms underpinning ARDS induced by COVID-19 are mostly immune-mediated, but need to be completely clarified. This study aimed to investigate redox balance in COVID-19 patients with ARDS, trying to recognize possible differences from typical ARDS related to the pathophysiology of severe disease.MethodsPatients affected by ARDS and positive for the SARS-CoV-2 virus (N= 40, COVID-19) were compared to ARDS patients negative to the molecular test (N= 42, No COVID-19). Circulating markers of redox balance were measured in serum and erythrocytes, and related to markers of inflammation and coagulability.ResultsNo differences in serum markers of oxidative damage were found between both groups, but a reduction in total antioxidant status and serum ceruloplasmin level was observed in COVID-19 rather than No COVID-19 patients. Redox balance alterations were described in erythrocytes from COVID-19 with respect to No COVID-19 group, characterized by increased lipofuscin and malondialdehyde concentration, and reduced glutathione S-transferase and glutathione reductase activity. These markers were associated with circulating indexes of respiratory disease severity (Horowitz index and alveolar-to-arterial oxygen gradient), inflammation (interleukin-6 and interleukin-10), and hypercoagulability (D-dimer) in COVID-19 patients with ARDS.ConclusionsARDS caused by COVID-19 is sustained by impairment of redox balance, particularly in erythrocytes. This alteration is associated with the pro-inflammatory and pro-coagulant status which characterizes severe COVID-19.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40560-023-00679-y.