The purpose of this study was to examine the effect of adding an essential fatty acid mixture (EOM; Eucalyptus globulus Labill, thymus vulgaris, Cymbopogon nardus, and Syzygium aromaticum) to the drinking water in the heat stress broilers on the adipokine (Apelin, BDNF) response, the histopathologic changes in liver and intestines, and some biochemical parameters. This study lasted for a total of 42 days, including the physical exercise period (7 days) and the fattening period (35 days). A total of 400 Ross 308 male broilers (1-d-old) were randomly divided into 8 groups (50 animals per group), each of which was exposed to various conditions of temperature (C: 22 C and SC: 36 C) and treatment dose (C, 250, 500 and 750 mL/1000 L). Each group was divided into 5 subgroups, each comprising 10 animals. In the stress-free groups, whereas the Apelin level linearly decreased, the BDNF level linearly increased. In histopathology, the liver tissue was found to be normal in all groups whereas the duodenum villi length was found to increase in the group of 750 mL/1000 L. No statistically significant difference was found between the stressed groups and the non-stressed groups in terms of VLDL, Glucose, Total bilirubin, ALT, and TG (p > .05). While Apelin level increased in the stressed groups, the BDNF level increased in the group of 250 mL/1000 L. In the histopathological examination, a small amount of coagulation necrosis was detected in hepatocyte, a diffuse hydropic degeneration was observed in hepatocytes, and finally a dilatation and hyperaemia were seen in sinusoid in the groups of EOM-500 mL/1000 L and EOM-750 m/1000 L compared to the control group. Whereas there was no difference between the group of EOM-250 mL/1000 L and the control group in terms of duodenum villa length, there was a significant decrease in other groups (p < .00). In conclusion, this study showed that adding 250 mL/1000 L of EOM to the drinking water had a positive effect on the serum levels of Apelin and p-BDNF in the groups exposed to stress (p <.05). HIGHLIGHTS Heat stress results in serious annual economic losses in the poultry industry. Essential oil fatty mix acids have positive effects on poultry health. Apelin and BDNF may be a protective factor against deleterious consequences of chronic exposition to heat stress ARTICLE HISTORY