Salmonella enterica serovar Enteritidis (S. Enteritidis) is a common zoonotic pathogen that not only causes gastroenteritis or death of livestock and poultry but also poses a serious threat to human health, causing severe economic losses to the poultry industry and society. Herein, RNA-sequencing (RNA-seq) was used to analyze the transcriptome variation of chicken cecum at four different time points (1, 3, 7, and 14 days) following S. Enteritidis infection. There were 529, 1477, 476, and 432 differentially expressed genes (DEGs) in the cecum at four different days post-infection (dpi), respectively. The DEGs were significantly enriched in various immune-related pathways on 3 dpi and 7 dpi, such as cytokine-cytokine-receptor interaction and Toll-like receptor signaling pathway. DEGs were significantly enriched in several metabolic pathways on 14 dpi. Gene ontology (GO) enrichment of DEGs showed that up-regulated genes were significantly enriched in immune-related terms on 3 and 7 dpi. On 14 dpi, up-regulated genes were mainly enriched in the signaling-related terms, while the down-regulated genes were primarily enriched in the metabolic-related terms. Based on weighted gene co-expression network analysis (WGCNA), the key modules related to energy, non-coding processes, immunity, and development-related functions were identified at 1, 3, 7, and 14 dpi, respectively, and 5, 8, 6, and 5 hub genes were screened out, respectively. This study demonstrated that the chicken cecal transcriptome regulation responding to S. Enteritidis infection is time-dependent. The regulation of S. Enteritidis infection in chickens is coordinated by multiple systems, mainly involving immunity, metabolism, and signal transduction. Both 3 and 7 dpi are key time points for immune response. As the infection progresses, metabolism-related pathways were increasingly identified. This change reflects the dynamic adjustment between immune response and metabolism in Jining Bairi chickens following S. Enteritidis infection. These results suggested that starting from 3 dpi, the chickens gradually transition from an immune response triggered by S. Enteritidis infection to a state where they adapt to the infection by modulating their metabolism.