Early diagnosis and treatment of sepsis in patients are crucial for their survival and can help reduce mortality rates. Novel biomarkers, such as thrombomodulin and pentraxin-3, have been used as diagnostic, prognostic and mortality indicators in patients with sepsis. Plasma thrombomodulin is a vascular endothelial membrane-bound glycoprotein and pentraxin-3 is an acute-phase protein. In the present study, thrombomodulin and pentraxin-3 levels were determined in calves with sepsis, to determine their diagnostic values as well as usefulness as indicators of health status. To this end, 20 neonatal calves with sepsis (G1) and ten healthy neonatal calves (G2) were used. Additionally, group G1 was also divided into two groups consisting of surviving (G1-S; n = 9) and non-surviving calves (G1-NS; n = 11). A single blood sample was collected from all the calves and the prepared serum samples were used to measure thrombomodulin and pentraxin-3 levels using bovine-specific ELISA kits. The serum concentrations of thrombomodulin and pentraxin-3 were found to be significantly higher (P < 0.01) in the G1 group than in G2. Thrombomodulin and pentraxin-3 levels were also found to be higher in the G1-NS group than in G1-S but the difference was not significant. We conclude that thrombomodulin and pentraxin-3 may have some diagnostic value in calves with sepsis. Furthermore, these findings may also help in understanding the pathogenesis of sepsis in neonatal calves. Further studies are required to determine the importance of thrombomodulin and pentraxin-3 as diagnostic and prognostic biomarkers in calves with sepsis and to evaluate the concentrations of these biomarkers also in other disease states.Keywords: haematology; leucocytosis; biomarker; acute-phase protein; neonatal calves List of abbreviations CRP = C-reactive protein, CRT = capillary refill time, DIC = disseminated intravascular coagulation, GRA = granulocyte, HCT = haematocrit, MAP = mean arterial pressure, PLT = platelet, PTX3 = pentraxin-3, RBC = red blood cell, SEM = standard error of the mean, SpO 2 = peripheral oxygen saturation, TLR = toll-like receptor, TM = thrombomodulin, WBC = white blood cell