Dairy cows experience stress at many times in their life and these stressful events increase the risk for negative health and productive outcomes. A better understanding of what causes stress and the impacts on the immune system will aid in developing management strategies that either reduce stress or attenuate the risk for disease. Cows are creatures of habit and this consistency gives her control. Take away this control and the more stressed she becomes. Stress generally suppresses many inflammatory leukocyte, neutrophil, and lymphocyte responses that create holes in the immune system, which microorganisms capitalize on to cause disease. An early lactating dairy cow is a great example of homeorhesis, whereas she is able to adapt to a new physiological state and environmental conditions. However, when that change is abrupt and/or dramatic, such as parturition and initiation of lactation, the cow can become stressed because the adaptation lags. The metabolic demands during the initiation of lactation play a major role in the dysfunctional immune system, and the effects are likely both direct and indirect. Direct effects are considered if nutrient demands of leukocyte responses are not met / prioritized or an increase in a metabolite, such as NEFA or BHBA, inhibits leukocyte function. Another example of a direct effect would be the negative effect of hypocalcemia on neutrophil function. The indirect effects are considered the physiological adaptations that need to occur in the cow that causes stress because they are a significant deviation and happen abruptly. Since some of the stress during the transition period is unavoidable, the focus should be to limit microbial exposure and any additional stressors that may have additional negative effects on immunity. Some factors that can contribute to additional stress include: high stocking density, poor cow comfort, dirty environment, comingling cows and heifers, and poor feed and bunk management. It is called the transition period because many changes are occurring and this increases the risk for stress. The stressors are multifactorial; therefore, a systematic approach to improving transition cow health is required.