A 75-year-old woman with infective endocarditis developed critical illness polyneuropathy (CIP) with quadriplegia after cardiac surgery. The quadriplegia resolved gradually after aggressive treatment of the underlying infection and with rehabilitation. However, a MEDLINE search of the English-language literature failed to yield results matching quadriplegia and infective endocarditis. CIP is a complication of septic syndrome and sepsis. This complication has been largely unrecognized in intensive care units owing to difficulties in performing a clinical examination or electrophysiologic studies. Difficulty in weaning from the ventilator is an important early manifestation of CIP. Electroneuromyography (ENMG) should be routinely performed to establish the diagnosis. We suggest that any septic patients with unexplained muscle weakness, paralysis, or difficulty in weaning from the ventilator should be evaluated for CIP.