Although the toxicological impact of metal oxide nanoparticles has been studied for the last few decades on aquatic organisms, the exact mechanism of action is still unclear. The fate, behavior, and biological activity of nanoparticles are dependent on physicochemical factors like size, shape, surface area, and stability in the medium. This study deals with the effect of nano and bulk CeO particles on marine microcrustacean, Artemia salina. The primary size was found to be 15 ± 3.5 and 582 ± 50 nm for nano and bulk CeO (TEM), respectively. The colloidal stability and sedimentation assays showed rapid aggregation of bulk particles in seawater. Both the sizes of CeO particles inhibited the hatching rate of brine shrimp cyst. Nano CeO was found to be more toxic to A. salina (48 h LC 38.0 mg/L) when compared to bulk CeO (48 h LC 92.2 mg/L). Nano CeO-treated A. salina showed higher oxidative stress (ROS) than those treated with the bulk form. The reduction in the antioxidant activity indicated an increase in oxidative stress in the cells. Higher acetylcholinesterase activity (AChE) was observed upon exposure to nano and bulk CeO particles. The uptake and accumulation of CeO particles were increased with respect to the concentration and particle size. Thus, the above results revealed that nano CeO was more lethal to A. salina as compared to bulk particles.