Objectives The primary target is to reveal whether the resuscitation with hypertonic saline (HTS) or hydroxyethyl starch (HES) would have different effects on the myeloid-derived suppressor cell (MDSC) count and monocytic MDSC (M-MDSC)/granulocytic/neutrophilic MDSC (G-MDSC) rate in the peripheral blood, spleen, and bone marrow nucleated cells (BMNC) in a controlled hemorrhagic shock mouse model under secondary Escherichia coli bacterial infection attack, comparing to resuscitation with normal saline (NS) in 72 hours. Method After hemorrhagic shock with bacteremia, which is induced by Escherichia coli bacterial infection attack, comparing to resuscitation with normal saline (NS) in 72 hours. Method. After hemorrhagic shock with bacteremia, which is induced by Escherichia coli 35218 injection, the mice were distributed into control, NS, HTS, and HES groups. The peripheral blood nucleated cells (PBNC), spleen single-cell suspension, and bone marrow nucleated cells were collected. The flow cytometry was used to detect the MDSC, M-MDSC, and G-MDSC. Result In PBNC, after resuscitation with NS, the MDSC was continuously higher, while the rate of M-MDSC/G-MDSC were continuously lower (P < 0.05). In HTS, the MDSC varied, higher at 24 and 72 hours (P < 0.05). In HTS, the MDSC varied, higher at 24 and 72 hours (P < 0.05). In HTS, the MDSC varied, higher at 24 and 72 hours (P < 0.05). In HTS, the MDSC varied, higher at 24 and 72 hours (P < 0.05). In HTS, the MDSC varied, higher at 24 and 72 hours (P < 0.05), the M-MDSC/G-MDSC were continuously lower (P < 0.05). In the spleen, resuscitation with HTS, the M-MDSC/G-MDSC were continuously lower (P < 0.05). In BMNC, after resuscitation with HES, the M-MDSC/G-MDSC were lower at 24 and 72 hours (P < 0.05). Conclusion In mouse hemorrhagic shock model with bacterial infection, the resuscitation with NS, HTS, or HES induced difference changes in MDSC and M-MDSC/G-MDSC, which were time-dependent and organ-specific. Resuscitation with crystalloid, like NS or HTS, showed longer effects on the MDSC and M-MDSC/G-MDSC in peripheral blood; while HTS has a longer effect on M-MDSC/G-MDSC in the spleen, HES has a stronger impact on the differentiation regulation of MDSC to G-MDSC in the bone marrow.