ObjectiveTo assess the incidence and determinants of ICU-acquired muscle weakness (ICUAW) in adult patients with enteral nutrition (EN) during the first 7 days in the ICU and mechanical ventilation for at least 48 hours.MethodsA prospective, nationwide, multicentre cohort study in a national ICU network of 80 ICUs. ICU patients receiving invasive mechanical ventilation for at least 48 hours and EN the first 7 days of their ICU stay were included. The primary outcome was incidence of ICUAW. The secondary outcome was analysed, during days 3–7 of ICU stay, the relationship between demographic and clinical data to contribute to the onset of ICUAW, identify whether energy and protein intake can contribute independently to the onset of ICUAW and degree of compliance guidelines for EN.Results319 patients were studied from 69 ICUs in our country. The incidence of ICUAW was 153/222 (68.9%; 95% CI [62.5%-74.7%]). Patients without ICUAW showed higher levels of active mobility (p = 0.018). The logistic regression analysis showed no effect on energy or protein intake on the onset of ICUAW. Overfeeding was observed on a significant proportion of patient-days, while more overfeeding (as per US guidelines) was found among patients with obesity than those without (42.9% vs 12.5%; p<0.001). Protein intake was deficient (as per US/European guidelines) during ICU days 3–7.ConclusionsThe incidence of ICUAW was high in this patient cohort. Early mobility was associated with a lower incidence of ICUAW. Significant overfeeding and deficient protein intake were observed. However, energy and protein intake alone were insufficient to explain ICUAW onset.Relevance to clinical practiceLow mobility, high incidence of ICUAW and low protein intake suggest the need to train, update and involve ICU professionals in nutritional care and the need for early mobilization of ICU patients.