The two oxidation states of ceria nanoparticles, Ce³⁺ and Ce⁴⁺, play a pivotal role in scavenging reactive oxygen species (ROS). In particular, Ce³⁺ is greatly responsible for eliminating O₂ ^- and ㆍOH that are associated with inflammatory response and cell death. Here, we report the synthesis of 2 nm ceria-zirconia nanoparticles (CZ NPs) possessing a higher ratio of Ce³⁺-to-Ce⁴⁺ and faster shifting from Ce⁴⁺ to Ce³⁺ than those exhibited by ceria nanoparticles. The obtained Ce_0.7Zr_0.3O₂ (7CZ) NPs markedly enhance their ROS scavenging performance, thus regulating inflammatory cells in a very low dose which is not possible with ceria nanoparticles. Furthermore, 7CZ NPs are demonstrated to be powerful for reducing mortality and systemic inflammation in two sepsis models. These findings suggest that 7CZ NPs have the potential as a therapeutic nanomedicine for treating ROS-related inflammatory diseases.