Dissolved oxygen (DO) is one of the most useful indices of river's health and the stream re-aeration coefficient is an important input to computations related to DO. Normally, this coefficient is expressed as a function of several variables, such as mean stream velocity, shear stress velocity, bed slope, flow depth, and Froude number. However, in free surface flows, some of these variables are interrelated, and it is possible to obtain simplified stream re-aeration equations. In recent years, different functional forms have been advanced to represent the re-aeration coefficient for different data sets. In the present study, the artificial neural network (ANN) technique has been applied to estimate the re-aeration coefficient (K 2 ) using data sets measured at different reaches of the Kali River in India and values obtained from the literature. Observed stream/channel velocity, bed slope, flow depth, cross-sectional area and re-aeration coefficient data were used for the analysis. Different combinations of variables were tested to obtain the re-aeration coefficient using an ANN. The performance of the ANN was compared with other estimation methods. It was found that the re-aeration coefficient estimated by using an ANN was much closer to the observed values as compared with the other techniques.