There are a variety of situations in an animal’s life when nutrient utilization is reprioritized from productive towards agriculturally unproductive purposes. Two well-known examples that markedly reduce production are heat stress and ketosis. Decreased feed intake, experienced during both disorders, is unable to fully explain production losses. Additionally, both disorders are characterized by negative energy balance, body weight loss, inflammation, and liver fat accumulation. While the metabolism of ketosis and heat stress has been thoroughly studied for the last 40 years, the initial insult in the cascade of events ultimately reducing productivity in both heat-stressed and ketotic cows has not been identified. To that end, we have generated preliminary data strongly implicating a metabolic disruptor, endotoxin, as the underlying cause in each case.