Administrating lipopolysaccharide (LPS) decreases circulating calcium (Ca) and markedly reduces both feed intake and milk yield in lactating cows. Calcium is involved in immune system activation and live yeast can increase feed intake. Whether supplemental live yeast and Ca benefits immune-challenged cows remains unclear. Therefore, study objectives were to evaluate if providing an oral supplement containing soluble Ca, live yeast and other micronutrients would ameliorate LPS-induced hypocalcemia and production parameters in lactating dairy cows. Providing an oral supplement containing Ca and live yeast prior to and following LPS administration markedly ameliorated the LPS-induced hypocalcemia and improved DMI and milk yield. Overall, utilizing an oral supplement may be a valuable management strategy to improve animal welfare and productivity during and following immunoactivation. Additionally, infusing i.v. LPS appears to be an effective technique to model hypocalcemia and to evaluate dietary strategies aimed at increasing circulating calcium in lactating dairy cows.