[Objective] With the universal application of CeO2 nanoparticles (CeO2 NPs), its biological toxicity and environmental effect have been paid more and more attention. The purpose of this study was to acquire the process and influence of CeO2 NPs on activated sludge from activated microorganisms metabolites. [Methods] EPS and SMP are the two main types of microbial metabolites, the content and composition of which were both examined after dosing different concentrations of CeO2 NPs in laboratory-scale activated sludge. [Results] The content of EPS and SMP increased with the increasing dosage of CeO2 NPs during a short period. The content of TB-EPS and LB-EPS didn’t have changed observably at low concentration of CeO2 NPs. The content of TB-EPS and its compositions were not significantly affected, while the polysaccharide and protein of LB-EPS increased for resistant to the toxicity of CeO2 NPs (more than 25 mg/L). Compared to the control upon exposure to CeO2 NPs (50 mg/L), the protein and polysaccharide increased 35.18% and 46.57% respectively. The content of two types of EPS increased in the presence of CeO2 NPs, and LB-EPS increased significantly higher than the LB-EPS growth. When the concentration of CeO2 NPs was more than 25 mg/L, the content of protein of SMP appeared, polysaccharide and humic also increased significantly as well. [Conclusion] The protein generated from SMP might be combined with nanometer materials to reduce the toxicity of nanomaterials. At the low concentration of CeO2 NPs, the adsorption effect of EPS would prevent CeO2 NPs from passing into the cell. However, when the concentration was higher, CeO2 NPs would stimulate the microorganisms to produce more EPS which could form a thicker outer barrier layer to protect cells better. EPS and SMP worked together to resist the toxicity of CeO2 on microbial cell.