ABSTRACT Avian coccidiosis, an intestinal parasitic disease caused by Eimeria spp., remains one of the most economically significant diseases in poultry. Although anticoccidial drugs have been effective in controlling coccidiosis, the emergence of drug resistance in Eimeria poses a persistent challenge to disease management. Our previous study revealed differential expression of superoxide dismutase ( Et SOD) between drug‐sensitive (DS) and drug‐resistant Eimeria tenella strains. In this study, qPCR and western blot analyses demonstrated that Et SOD expression was significantly upregulated in diclazuril‐resistant (DZR) and maduramicin‐resistant (MRR) strains compared to the DS strain, with a progressive increase corresponding to higher drug concentrations. Enzyme activity assays further confirmed that SOD activity was elevated in both resistant strains. Additionally, qPCR results indicated higher Et SOD mRNA levels in second‐generation merozoites and unsporulated oocysts than in sporulated oocysts and sporozoites. Indirect immunofluorescence revealed that fluorescence intensity increased during parasite development within host cells. Notably, Et SOD was predominantly localized on the surface of sporozoites and merozoites, as well as on the parasitophorous vacuole membrane (PVM) post‐invasion of DF‐1 cells, suggesting its potential role in host–parasite interactions and immune evasion. Collectively, these findings imply that Et SOD may contribute to drug resistance and facilitate parasite growth and development within host cells.