Four buffalo calves were available for this study, aged six months and weighed (BW) 118.0 – 119.0 kg at Animal Physiology Research Lab, Animal Production Department, Faculty of Agriculture, Cairo University. The present work aimed to compare between the effect of heat shock on buffalo calves to 1st and 2nd acute response under exposure to artificial constant heat stress (40°C). and a comparatisia between 1st and 2nd acute response of buffalo calves for response of thermo-respiratory responses, hematological response, plasma metabolites, hormones, feed intake and water intake. The results obtained from this study could be summarized as follows to found reaction of buffalo calves to acute physiological response of the 2nd shock to thermal condition at 40°C it is found that all parameters were best comparative with the 1st shock. Stability of RR under this condition during the 2nd shock indicator to the buffalo can be heat tolerance over, the white blood cells count increased as an indication of immunological activity, the values of globulin during two shocks were not significant confirm the higher immunity for buffaloes. Values of water consumption/day in two trails were not significant, for zero and trails shock may be indicator to tolerance the buffalo calves decreased the water and this trend needs more study. It could be concluded that stability of buffalo calves under this condition cousideved as an indicator to the beast animal with climatic change