Objective To explore the possible causes of susceptibility to multiple pathogens in CAST/EiJ mice, immune cell phenotypes in the peripheral blood and spleen of CAST/EiJ mice were analyzed to clarify the immune cell composition of CAST/EiJ mice. Methods Classical dendritic cells (cDCs), natural killer (NK) cells, B lymphocytes, T lymphocytes and their subsets in 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 was low. The proportion of NK cells (mainly mature NK cell subsets) and T lymphocytes (mainly CD8+ T cells) were both lower in CAST/EiJ mice than in C57BL/6J mice, while the proportion of B cells in CAST/EiJ mice were higher than those in C57BL/6J mice. Conclusion The proportion of NK and T lymphocytes in CAST/EiJ mice was lower than those in C57BL/6J mice.