In this paper, a fault diagnosis method for the basic process of microbial growth in wastewater treatment based on interval estimation technology is proposed. First, a nonlinear microbial growth model is converted into a linear time‐varying system. A time‐varying observer is then designed for the generated system, which takes into account an performance. Furthermore, a zonotope‐based set‐membership estimation algorithm is analyzed to synchronize interval estimation operations. In addition, interval residuals are computed from the generated interval state estimation and fault diagnosis is performed for a wastewater treatment bioprocess with sensor fault signals. Finally, the feasibility of the proposed fault diagnosis strategy for the wastewater treatment bioprocess is illustrated through numerical simulations.