Background <p>COVID-19 has emerged as a complex disease extending beyond respiratory involvement and is characterized by systemic inflammation and oxidative stress, which may also affect the cardiovascular system. Our study sought to elucidate the function of biomarkers serum myeloperoxidase (MPO), ischemic modified albumin (IMA), paraoxonase-1 (PON-1) and galectin-3 (GAL-3) in the pathophysiology of COVID-19 to explore their potential associations with pathophysiological mechanisms commonly involved in myocardial injury.</p> Methods <p>Our prospective case-control study assessed biomarker discrimination between hospitalized COVID-19 patients and healthy controls. Serum levels of biomarkers were measured using ELISA and enzymatic reaction products were assessed using spectrophotometric methods.</p> Results <p>Our findings showed that serum MPO, IMA, and GAL-3 levels were significantly higher in the COVID-19 group compared with control, while PON-1 levels were significantly lower. Subgroup analyses based on disease severity revealed that changes in these biomarkers were more pronounced in patients with severe COVID-19.</p> Conclusions <p>The significant increase in GAL-3 and MPO levels in severe cases supports the role of inflammatory burden and oxidative stress in disease progression, while the decrease in PON-1 levels indicates a decrease in antioxidant defense capacity. Overall, these findings indicate the presence of shared pathophysiological mechanisms between COVID-19 and myocardial injury, rather than providing direct evidence of myocarditis. The observed biomarker alterations are compatible with mechanisms implicated in myocarditis and may be of interest for future myocarditis research; however, direct evaluation in well-characterized myocarditis cohorts is required.</p>