The use of intrathecal clonidine as an adjunct for the management of chronic pain, intra- and postoperative analgesia is gaining an increase in popularity. However, antinociceptive doses of intrathecal clonidine may produce pronounced hemodynamic side effects, including hypotension and bradycardia. In this report, we present a case of severe hypotension after cardiopulmonary bypass in a patient with intrathecal clonidine infusion. We postulate that the intrathecally administered alpha 2-agonist clonidine reduced our patient's ability to tolerate the hemodynamic lability that is present during the separation from cardiopulmonary bypass by potentially inhibiting sympathetic nervous system activity, renin-angiotensin system, or vasopressin release. The authors report a case of severe hypotension after cardiopulmonary bypass in a patient receiving intrathecal clonidine infusion for chronic neuropathic pain.