The objective of recurrent study was to determine the some clinicopathological (hematological and biochemical) changes in native buffalo calves (aged between 1-15 day) infected with enterotoxigenic E. coli (ETEC) K99 + detected by direct ELISA, during the period between September 2018-April 2019. A total of 40 fecal samples (30 samples from infected animal and 10 samples from clinically healthy Buffalo calves) was examined by direct ELISA. Six samples form diarrheic animals (20%) were positive for E. coli (K99). The blood gas analysis of blood samples revealed significant decrease in the means of the blood pH, Partial pressure of oxygen concentration (PO 2), Partial pressure of carbon dioxide concentration (PCO 2), base excess (BE), as well as electrolytes: sodium (Na +), chloride (CL-), bicarbonate (HCO 3-), calcium (Ca ++) and nonionized calcium (nCa ++) ions concentrations, while a significant increase in the mean of hemoglobin concentration (tHB), packed cell volume (PCV) and anion gap (AG) in the buffalo calfs infected with enterotoxigenic E. coli (ETEC) K99 + comparison with the control animals. The main clinicopathological changes in native buffalo calves infected with enterotoxigenic E. coli (ETEC) K99 + were significantly decrease in electrolytes, blood gases, Calcium (Ca ++) and nonionized Calcium (nCa ++) ions concentrations.