Background: Muscle weakness in the intensive care unit (ICU), referred to as ICU-acquired weakness (ICUAW), is a common complication observed in patients receiving mechanical ventilation. This study aimed to investigate whether rehabilitation intensity and nutrition during ICU admission are associated with the incidence of ICUAW.Materials and methods: Consecutive patients aged ≥18 years who were admitted to the ICU between April 2019 and March 2020 and who received mechanical ventilation for >48 h were eligible. The included patients were divided into two groups: the ICUAW group and the non-ICUAW group. ICUAW was designated by a Medical Research Council score of less than 48 during discharge from the ICU. Patient characteristics, time to achieve ICU mobility scale (IMS) 1 and IMS 3, calorie and protein deliveries, and blood creatinine and creatine kinase levels were evaluated as study data. In this study, the target dose for the first week after admission to the ICU at each hospital was set at 60-70% of the energy requirement calculated by the Harris-Benedict formula. Univariate and multivariate analyses were used to determine the odds ratios (OR) for each factor and to explain the risk factors for the occurrence of ICUAW at ICU discharge.Results: During the study period, 206 patients were enrolled; 62 of the 143 included patients (43%) had ICUAW. The results of multivariate regression analysis showed that low time to IMS 3 achievement (OR 1.19, 95% confidence interval (CI) 1.01-1.42, p=0.033), and high mean calorie (OR 0.83, 95% CI 0.75-0.93, p<0.001) and protein deliveries (OR 0.27, 95% CI 0.13-0.56, p<0.001) were independently associated with the occurrence of ICUAW.Conclusions: Increase in rehabilitation intensity and mean calorie and protein deliveries were associated with a decrease in the occurrence of ICUAW at ICU discharge. Further research is required to validate our results. Our observations, increasing the intensity of physical rehabilitation and the average calorie and protein delivery levels during ICU stay, appear to be the preferred strategies for achieving non-ICUAW.