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No previous study has demonstrated whether critical illness polyneuropathy itself lengthens mechanical ventilation or whether this prolonged duration of ventilatory support is explained by concomitant risk factors for weaning failure. Our objectives were to evaluate the impact of critical illness polyneuropathy on the length of mechanical ventilation after controlling for coexisting risk factors for weaning failure and to assess the impact of critical illness polyneuropathy on the length of the stay in a cohort of septic patients.Prospective cohort study.Intensive care unit of a tertiary hospital.All patients with severe sepsis or septic shock who required mechanical ventilation for ≥7 days who were considered ready to discontinue mechanical ventilation.Patients underwent a neurophysiologic evaluation at onset of weaning from mechanical ventilation.Sixty-four critically ill septic patients were enrolled, and 34 developed critical illness polyneuropathy (53.1%; 95% confidence interval, 40.2–65.7%). Length of mechanical ventilation was significantly higher in patients who had developed critical illness polyneuropathy (median 34 days vs. 14 days, p < .001). The duration of the weaning period was also significantly greater in patients with critical illness polyneuropathy (median 15 days vs. 2 days, p < .001) even though factors suspected to influence the weaning process did not differ between these two groups. Multiple logistic regression analysis indicated that critical illness polyneuropathy was the only risk factor independently associated with weaning failure (odds ratio, 15.4; 95% confidence interval, 4.55, 52.3; p < .001). Lengths of intensive care unit and hospital stays were significantly higher in patients with critical illness polyneuropathy.In critically ill septic patients, critical illness polyneuropathy significantly increases the duration of mechanical ventilation and prolongs the lengths of intensive care unit and hospital stays.