— This paper deals with the state estimation of nonlinear systems. The systems under study are characterized by two-time scale models. The state estimation is performed by designing a proportional integral observer (PIO) with unknown inputs. In order to design such an observer, the nonlinear model is transformed into an equivalent multiple model form and the fast dynamics are considered as unknown inputs. An application to an ASM1 model of Wastewater Treatment Plants (WWTP) is considered and the obtained numerical results show the performances of the proposed approach.