<p><i>Eimeria tenella</i> (<i>E. tenella</i>) infection is a major cause of coccidiosis in chickens, leading to significant economic losses in the poultry industry due to its impact on the cecum. This study presents a comprehensive single-cell atlas of the chicken cecal epithelium by generating 7,394 cells using 10X Genomics single-cell RNA sequencing (scRNA-seq). We identified 13 distinct cell types, including key immune and epithelial populations, and characterized their gene expression profiles and cell–cell communication networks. Integration of this single-cell data with bulk RNA-seq data from <i>E. tenella</i>-infected chickens revealed significant alterations in cell type composition and state, particularly a marked decrease in <i>APOB</i>⁺ enterocytes and an increase in cycling T cells during infection. Trajectory analysis of <i>APOB</i>⁺ enterocytes uncovered shifts toward cellular states associated with cell death and a reduction in those linked to mitochondrial and cytoplasmic protection when infected with <i>E. tenella</i>. These findings highlight the substantial impact of <i>E. tenella</i> on epithelial integrity and immune responses, emphasizing the parasite’s role in disrupting nutrient absorption and energy metabolism. Our single-cell atlas serves as a critical resource for understanding the cellular architecture of the chicken cecum and provides a valuable framework for future investigations into cecal diseases and metabolic functions, with potential applications in enhancing poultry health and productivity.</p>