Objective To evaluate the effect of murine norovirus (MNV) infection on immune function in miceby assessing the changes in peripheral blood immune parameters. Methods KM, BALB/ c, BALB/ c-nu, C57BL/6, andNIH mice were selected. Each strain was divided into an MNV infection group and a control group. Anticoagulated bloodsamples were collected from the periocular vein plexus before infection (day 0) and at 7, 14, 21, and 28 d post-infection.Flow cytometry was used to determine the percentage of total T cells, CD4⁺ T cells, CD8⁺ T cells, total B cells, NK cellsand NK-T cells in the total lymphocytes and the levels of 13 cytokines such as interferon and interleukin, and chemokines.To compare the differences in the mean values of each index after infection, the changes at each time point were analyzed.Results Compared with the control group, the level of total T cells and CD4⁺ T cells in the infected group of KM micesignificantly increased ( P <0. 01), CD4/ CD8 significantly increased ( P <0. 05), and the total B cell and CXCL10 contentsignificantly decreased ( P <0. 01). The level of CD8⁺ T cells in infected BALB/ c mice significantly decreased ( P <0. 05),and IFN-γ levels significantly increased ( P <0. 01). There was no significant difference between the levels of immune cellsin infected and control BALB/ c-nu mice, although in the infected BALB/ c-nu mice TNF-α, CXCL1 and CXCL10significantly increased ( P <0. 01), CCL2 significantly increased ( P < 0. 05), and IFN-β significantly decreased ( P <0. 05). CD4⁺( P <0. 05) and CD8⁺ T cells ( P <0. 01) in the infected C57BL/6 mice significantly decreased, total B cellsand IL-10 significantly increased ( P <0. 05), and CCL5 and GM-CSF significantly decreased ( P <0. 05). Total T cells andCD8⁺ T cells in the infected NIH mice significantly increased ( P <0. 01), CD4/ CD8 significantly decreased ( P <0. 05),and total B cells significantly decreased ( P <0. 01), while there were no significant differences in cytokine levels. In termsof statistically significant changes in immune indicators, half of all immune indicators showed significant differences on the7th day of infection, and most still demonstrated significant differences on the 28th day. Conclusions MNV infectionaffects cellular and humoral immune responses in otherwise healthy mice, and different mouse strains demonstrate differenteffects. Researchers should select MNV-negative mice in immunologically relevant animal experiments to avoid bias in the experimental results.