The objective of the present study is to investigate the role of heat shock proteins (Hsps) in preimplantation embryonic development and uterine receptivity during lipopolysaccharide (LPS)-induced pregnancy loss. Mice were treated with PBS or LPS on Day 0.5 of pregnancy, and preimplantation embryos and uterus were collected on Days 1.5–4.42 of pregnancy. The individual preimplantation embryos were assessed for their morphologic appearance and DNA damage during the preimplantation period of pregnancy. The expression of Hsp90, Hsp70, Hsp60, and Hsp25 was determined in preimplantation embryos and uterus by RT-PCR. Comet studies showed that LPS treatment significantly increased the percentage of abnormal embryos and DNA damage in the embryos. The expression of Hsp90, Hsp70, and Hsp60 was significantly lower in preimplantation embryos recovered from LPS-treated mice when compared to their respective controls. The expression of Hsp90, Hsp70, Hsp60, and Hsp25 was altered in uterus of LPS-treated mice when compared to their respective controls. Immunohistochemistry studies showed that at the time of implantation (i.e., Day 4.42), levels of Hsp90 and Hsp60 were decreased in stromal cells of LPS-treated uterus when compared to their respective controls. Hsp25 was highly expressed in the endometrium and stromal cells of LPS-treated uterus. Our results clearly showed that lowering of embryonic expression of Hsps induces DNA damage, which leads to degeneration and degradation of preimplantation embryos, and altered uterine expression of Hsps may not prepare the uterus for implantation. This may ultimately lead to implantation failure in mouse.