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A continuously stirred tank reactor (CSTR) is largely used in water treatment and in chemical and biological processes. It is characterized by a complex non‐linear behaviour. Operating large reactors in industry can be expensive, so a common trick used to reduce costs is to operate multiple CSTRs in series. Consequently, the CSTR is usually exposed to faults and noises. This paper addresses the design of a robust observer for estimation and fault diagnosis strategy on two CSTRs in series. The considered system is affected simultaneously by time‐varying actuator and sensor faults with measurement noises. The Takagi‐Sugeno multimodel approach is proposed to transform the non‐linear model into an interpolation of several linear sub‐models with non‐measurable premise variables. The purpose of this brief is to provide the state and the fault estimation for the considered system using a proportional multiple integral (PMI) unknown input observer. The exponential stability conditions are studied with the Lyapunov theory and L2 optimization and formulated in terms of linear matrix inequalities. In addition, a comparative study with a PMI observer is conducted. Finally, the proposed observer is used for time‐varying fault detection and isolation.

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