It is a well known fact that presence of heavy metal ions in wastewater reduces the performance of activated sludge systems. Removal of heavy metals from wastewater before biological treatment is a viable approach used to improve the biological treatment performance. One of the methods used for removal of heavy metals from wastewater is biosorption. Mathematical model was developed to describe the heavy metal ions inhibition in an activated sludge unit. Box-Behnken experimental design method was used to investigate heavy metal ions, chemical oxygen demand (COD) and toxicity removal performance of the activated sludge unit under different operating conditions.