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This article is from Journal of Environmental Health Science and Engineering , volume 12 . Abstract This paper examined the efficiency of multivariate linear regression (MLR) and artificial neural network (ANN) models in prediction of two major water quality parameters in a wastewater treatment plant. Biochemical oxygen demand (BOD) and chemical oxygen demand (COD) as well as indirect indicators of organic matters are representative parameters for sewer water quality. Performance of the ANN models was evaluated using coefficient of correlation (r), root mean square error (RMSE) and bias values. The computed values of BOD and COD by model, ANN method and regression analysis were in close agreement with their respective measured values. Results showed that the ANN performance model was better than the MLR model. Comparative indices of the optimized ANN with input values of temperature (T), pH, total suspended solid (TSS) and total suspended (TS) for prediction of BOD was RMSE = 25.1 mg/L, r = 0.83 and for prediction of COD was RMSE = 49.4 mg/L, r = 0.81. It was found that the ANN model could be employed successfully in estimating the BOD and COD in the inlet of wastewater biochemical treatment plants. Moreover, sensitive examination results showed that pH parameter have more effect on BOD and COD predicting to another parameters. Also, both implemented models have predicted BOD better than COD.