BACKGROUND: Critical illness myopathy and/or neuropathy (CRIMYNE) is a common alteration seen in the ICU. The currently available bedside methods of measuring respiratory and peripheral muscle function in critically ill patients are somewhat inadequate. The objective of this study was to evaluate the presence of diaphragmatic and peripheral CRIMYNE in septic patients with prolonged weaning from mechanical ventilation (MV). METHODS: Cohort prospective study with an entry period of 6 months. In 2 Brazilian medical-surgical ICUs, septic patients ≥ 18 years of age, dependent on MV ≥ 14 days, requiring prolonged weaning from MV, awake (Richmond Agitation Sedation Scale ≥ -2), and with no previous history of polyneuropathy or myopathy were included. Electrophysiological studies of the limbs and also of the respiratory system by phrenic nerve conduction and needle electromyography of the diaphragm were performed in all subjects. RESULTS: Twelve subjects were enrolled during 6 months of study. The electrophysiological signs of peripheral CRIMYNE occurred in 9 subjects, 7 of whom died in the ICU. Three subjects developed critical illness polyneuropathy, 4 critical illness myopathy, and 2 both. Only one subject who developed peripheral CRIMYNE did not present diaphragmatic involvement, whereas no subject developed diaphragm involvement alone. Thus, electrophysiological signs of diaphragmatic CRIMYNE occurred in 8 of the 9 subjects with peripheral CRIMYNE. Upon clinical examination, 8 subjects were not able to moves their limbs against gravity, and these findings were related to the presence of peripheral and diaphragmatic dysfunction. CONCLUSIONS: Our pilot findings suggested that CRIMYNE is common in septic patients with prolonged weaning from MV (MV ≥ 14 d). The inability to move limbs against gravity is frequently associated with peripheral and diaphragmatic CRIMYNE, and the findings of CRIMYNE in peripheral electrophysiological tests are associated with diaphragmatic involvement.