© 2021, National Institute of Health. All rights reserved.It is important to determine the inflammatory biomarkers in the severity of coronavirus disease 2019 (COVID-19) with the emergence of the pandemic. Galectins and prostaglandins play important roles in the regulation of immune and inflammatory responses. Therefore, this study aimed to investigate Galectin-1 (Gal-1), Galectin-3 (Gal-3), and prostaglandin E2 (PGE2) levels in patients with COVID-19. Serum concentrations of Gal-1, Gal-3, and PGE2 were measured using enzyme-linked immunosorbent assay on 84 patients with COVID-19 (severe = 29 and nonsevere = 55) and 56 healthy controls. In this study, increased levels of Gal-1 (median, 9.86, 6.35, and 3.67 ng/mL), Gal-3 (median, 415.31, 326.33, and 243.13 pg/mL), and PGE2 (median, 193.17, 192.58, and 124.62 pg/mL) levels were found in patients with COVID-19 than in healthy controls (P < 0.001 for all). In the severe disease group, Gal-3 levels were higher, while no differences were noted in Gal-1 and PGE2 levels (P = 0.011, P = 0.263, and P = 0.921, respectively). Serum levels of Gal-1 were positively correlated with those of Gal-3 (P = 0.871 and P < 0.001). Gal-3, C-reactive protein, lymphocyte count, and age were found as independent predictors of disease severity (P = 0.002, P = 0.001, P = 0.007, and P = 0.003, respectively). With the emergence of effective drug needs in the COVID-19 pandemic, differentiation of severe disease is important. Therefore, Gal-3 could be a potential prognostic biomarker of COVID-19.