Changes in sleep quantity and quality, as well as the presence of delirium, are common in the ICU environment. Their presence plays a significant negative role in the outcome of ventilator weaning. Recognizing changes in sleep patterns and delirium, and understanding their characteristics and causes, are fundamental to mitigating their negative effects and ensuring the success of ventilator weaning. Ventilatory adjustments, environmental control, and the rational use of pharmacological treatments are critical allies in improving sleep quality in ICU weaned patients. Non-pharmacological strategies, such as virtual reality (VR) technology, are highly useful in controlling delirium, thereby improving the patient’s stay in the ICU and facilitating the proper progression of ventilator weaning.