A vital process in wastewater treatment is the biological treatment with activated sludge. In Romania, there are still plenty of cases where the biological treatment stage is operated manually, leading to inefficient operation and implicitly to higher operational costs, increased difficulty in maintaining the quality of the effluent and less disturbance rejection capabilities. In our paper, we show that using a medium-fidelity first principle model and by carrying out an RGA analysis, a decentralized control strategy using PI controllers can be easily developed and tested before implementation, the control strategy giving good results in disturbance rejection and trajectory tracking.