COVID-19 is an infectious respiratory disease caused by the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Raftlin is a large lipid raft protein found in cell membranes and plays a crucial role in inducing autoimmune and vascular inflammatory responses. Although there have been few studies on 8-iso-prostaglandin F2α (8-iso-PGF2α) as a marker of oxidative stress in COVID-19, the levels of raftlin in the disease have not been previously investigated. The objective of our study was to evaluate the levels of Raftlin and 8-iso-prostaglandin F2α (8-iso-PGF2α) in COVID patients. We analyzed clinical findings from three groups: healthy controls, patients with a mild course of COVID, and patients with a severe course of COVID. We measured the levels of Raftlin and 8-iso-PGF2α in serum samples using ELISA. Our results showed that the levels of Raftlin and 8-iso-PGF2α were higher in patients with severe COVID compared to the control and mild course groups. Furthermore, a significant positive correlation was found between Raftlin and 8-iso-PGF2α in the severe COVID group. Raftlin was identified as a potentially important biomarker in COVID-19 patients. This study is valuable as it is the first to investigate changes in Raftlin and 8-iso-PGF2α levels in COVID-19 disease.