In this study, it was aimed to conduct diagnostic evaluation of hematological indices (monocyte/lymphocyte ratio (MLR), erythrocyte distribution width (RDW), mean platelet volume (MPV)) and blood gas parameters (partial oxygen pressure (pO2), partial carbon dioxide pressure (pCO2), lactate, sodium (Na+), potassium (K+), chlorine (Cl-), bicarbonate (HCO3-) pH, anion gap (AG) and base excess (BE)) in calves with diarrhea associated sepsis. The study material consisted of two groups, 20 calves with sepsis (sepsis) which were 1-28 days old and presented with diarrhea and 10 healthy calves (control). Fecal samples obtained from calves diagnosed with systemic inflammatory response syndrome (SIRS) were analyzed for Rotavirus, Coronavirus, Escherichia coli, Cryptosporidium parvum and Giardia lamblia using immunochromatographic test kits. Total leukocyte count (WBC), lymphocyte (LYM), monocyte (MON), hematocrit (HCT), RDW and MPV, pO2, pCO2, lactate, Na+, K+, Cl-, HCO3-, pH, AG and BE parameters were measured. WBC (P<0.010), MON (P<0.001), MPV (P<0.001) and MLR (P<0.001) values of the sepsis group were statistically higher than the control group. In the sepsis group, pH (P<0.001), HCO3- (P<0.001) and BE (P<0.001) values were significantly lower than in the control group. K+ (P<0.003) and AG (P<0.001) concentrations were significantly higher in the sepsis group compared to the control group. In the diagnosis of sepsis, the area under the curve for MON was 0.895, with a sensitivity of 80% and specificity of 75%; for RDW, the area under the curve was 0.840, with a sensitivity of 80% and specificity of 75%; for MPV, the area under the curve was 0.915, with a sensitivity of 100% and specificity of 90%; for MLO, the area under the curve was 0.910, with a sensitivity of 80% and specificity of 80%. In conclusion, MPV and MLR parameters are considered to be valuable in the diagnosis of sepsis in calves.