A fundamental practice in process engineering is monitoring the state dynamics of a system. Unfortunately, observability of some states is related to high costs, time, and efforts. The mechanistic event recognition (MER) aims to detect an event (defined as a change of the system with specific significance to the operation of the process) that cannot be directly observed but has some predictable effect on the dynamics of the systems. MER attempts to apply fault diagnosis techniques using mechanistic “recognition” models to describe the process. A systematic method for building recognition models using optimal experimental design tools is presented. As proof of concept, the MER approach to detect organic matter depletion in sequencing batch reactors, measuring only ammonia, dissolved oxygen, and nitroxides is applied. The event, that is, consumption of organic matter to a level below 50 gCOD/m3, was successfully detected even though microbial activity is known to continue after organic matter depletion