ECMO is used to provide cardiopulmonary support to critically ill neonates. Vasopressin (VP) plays a vital role in regulating mean arterial pressure (MAP) and regional blood flow in hypotensive disorders, but whether endogenous VP levels can be sustained during ECMO is unclear. In this study, 11 anesthetized, cardiac catheterized piglets were put on veno‐arterial ECMO either during control or endotoxin‐induced septic shock states. ECMO blood flow was delivered to maintain MAP at baseline levels. Plasma VP (pVP) was compared before and after stabilization on ECMO for 2 hours. ECMO caused pVP to drop by 30% (p<0.01) in both control and septic shock conditions. This drop may be due to the ECMO circuit adding to total circulating volume without additional release of VP. To test whether right atrial pressure (RAP) influence on VP release may be disrupted during ECMO due to partial cardiac bypass of blood flow, the relationship between pVP and hemodynamics during control was examined with stepwise regression. Pre‐ECMO, pVP negatively correlated with RAP and heart rate (r=0.83, p<0.05), but not MAP. In contrast, during ECMO, this pVP relationship with RAP was lost, but a strong positive correlation (r=0.76, p<0.05) between pVP and MAP became evident. Results indicate that during ECMO, low pressure atrial baroreceptors no longer regulate VP release, but VP control of MAP is maintained. Supported by US Army CRADA 0709‐T‐C454