Abstract Toll-like receptor 4 (TLR4) signaling mediates sustained systemic inflammation in(COVID)-19 patients. We aimed to assess the serum levels of sTLR4 and sCD14 as negative regulators of Toll like receptor signaling and their association with laboratory markers and clinical severity in covid 19 patients. Ninety-eight patients with COVID-19 (70 severe and 28 non-severe) were enrolled in the study. Serum sCD14 andsTLR4were determined by ELISA. A significant increase in serum sTLR4 and sCD14 levels was detected in severe compared to non severe COVID19 patients.Receiver operating characteristic curve (ROC) analysis revealed significant diagnostic potential of serum sTLR4 and sCD14 in covid19 patients.We conclude that Serum sTLR4 and sCD14 may be promising clinical severity markers for COVID19 patients.