This paper describes a procedure to find the best controlled variables in an economic sense for the activated sludge process in a wastewater treatment plant, despite the large load disturbances. A novel dynamic analysis of the closed loop control of these variables has been performed, considering a nonlinear model predictive controller (NMPC) and a particular distributed NMPC-PI control structure where the PI is devoted to control the process active constraints and the NMPC the self-optimizing variables. The well-known self-optimizing control methodology has been applied, considering the most important measurements of the process. This methodology provides the optimum combination of measurements to keep constant with minimum economic loss. In order to avoid nonfeasible dynamic operation, a preselection of the measurements has been performed, based on the nonlinear model of the process and evaluating the possibility of keeping their values constant in the presence of typical disturbances. (C) 2015 Elsevier Ltd. All rights reserved.