Objective To explore the possible causes of CAST/ EiJ mouse susceptibility to multiple pathogens,the immune cell phenotypes in the peripheral blood and spleen of CAST/ EiJ mice were analyzed to clarify their composition. Methods Classical dendritic cells (cDCs), natural killer (NK) cells, B lymphocytes, T lymphocytes, and their subsets in the peripheral blood and spleen of CAST/ EiJ mice and C57BL/ 6J mice were detected by flow cytometry using the cell surface markers CD3, CD4, CD8, CD11b, CD11c, CD19, CD27, CD49b, and TCRβ. Results There was no significant difference in the proportion of cDCs between CAST/ EiJ and C57BL/ 6J mice, but the cDC1 cell subset population was smaller in CAST/ EiJ. The proportions of NK cells ( mainly mature NK cell subsets) and T lymphocytes(mainly CD8⁸⁺T cells) were both lower in CAST/ EiJ mice than C57BL/ 6J mice, while the proportion of B cells was higher in CAST/ EiJ mice than C57BL/ 6J mice. Conclusions The proportions of NK and T lymphocytes in CAST/ EiJ mice were lower than those in C57BL/ 6J mice.