This research is an attempt to study ecosystem reaction of Karkheh River and Hoor al-Azim Wetland against the changes in the flow regime of the river using Bayesian Network modelling approach. In this research, demographic changes of two fish species of Barbus Grypus and Barbus Sharpeyi, as two important ecological indicators in the region, against the stress caused by water flow fluctuations were investigated by the next 10 years. For this purpose, the Bayesian Network was structured by three sub-models of hydrology, ecology, and quality. Future trends of demographic changes were studied in the form of three scenarios, including the natural condition (before the construction of the dam), current situation (after its construction and operation), and the predicted (proposed) situation of Karkheh River discharge in the next 10 years with a focus on the drought and wet periods. According to the natural scenario, this model predicts a 60% probability that the Barbus Grypus population will increase or survive, which shows a 16% decrease compared to the current situation. Due to tangible changes in the volume of water flow in the spring and summer, spawning and larval transmission in the current conditions is reduced compared to natural conditions. As a result, the population of Barbus Grypus in the current situation is lower than that in normal conditions. Based on the proposed scenario, there is a 24% chance of maintaining or increasing the Barbus Grypus population for the next 10 years. No significant changes were observed under any of the scenarios in the population of Barbus Sharpeyi by the next decade.