The transition to lactation (3 weeks before to 3 weeks after calving) is characterized by a decrease in dry-matter intake (DMI), leading to a sharp decrease in glucose and calcium, and an increase in body fat mobilization in the form of non-esterified fatty acids (NEFA). This results in products such as betahydroxybutyrate (BHBA) accumulating from incomplete oxidation of NEFA (Vazquez-Añon et al., 1994). Neutrophils (PMN) are the main leukocyte type involved in clearing bacteria after uterine infection; however, during the period of negative energy balance, dairy cows experience a reduction in PMN function, including reduced phagocytosis and killing capacity. This reduction is more pronounced in cows that develop uterine disease. Glycogen is the main source of energy for PMN phagocytosis and killing; calcium is an important second messenger for PMN activation; NEFA is associated with impaired PMN oxidative burst activity; and BHBA reduces PMN phagocytosis, extracellular trap formation, and killing of bacteria. If the immune system is not able to eliminate bacterial infection, disease is established. Pathogenic bacteria associated with metritis and endometritis are E. coli, A. pyogenes, F. necrophorum, and P. maleninogenicus. E. coli increases the susceptibility of the endometrium to subsequent infection with A. pyogenes, and A. pyogenes acts synergistically with F. necrophorum and P. melaninogenicus to enhance the severity of uterine disease. Among their effects, E. coli releases bacterial-wall LPS; A. pyogenes produces the cholesterol-dependent cytotoxin pyolysin and a growth factor for F. necrophorum; F. necrophorum produces a leukotoxin; and P. melaninogenicus produces a substance that inhibits phagocytosis. A specific E. coli, called EnPEC/IUEC, causes uterine disease, and the virulence factor fimH was mostly associated with disease. For A. pyogenes, fimA was the only virulence factor associated with uterine disease. The combined effect of bacterial infection and activation of inflammation is damage to the endometrium and embryo, delayed ovulation, shortened or extended luteal phase after ovulation, increased time to first insemination, decreased conception rates, increased time to conception, and increased pregnancy loss.