Purpose: We aimed to determine the tongue edema that may develop due to the pressure exerted by the endotracheal intubation (ETI) tube on the tongue during the follow-up period of mechanical ventilation in patients intubated in the intensive care unit (ICU) by submental ultrasonography (USG). Also, we aimed to investigate the effect of tongue edema on the oxygen saturation values (SpO2) measured two h after extubation. Methods: One hundred patients aged 18–65 years, who were followed up with mechanical ventilation in the ICU from the 0th day of intubation, were included. Patients (n = 57) who were followed up on mechanical ventilation for four days or longer after ETI were included in the study group. Those who were followed up on mechanical ventilation for three days or less after endotracheal intubation and were extubated during this period were included in the control group (n = 43). The tongue cross-sectional areas (TSAs) of patients in both groups were measured twice with submental USG. The first measurement (TSA1) was performed on the 0th day of ETI in all patients in both groups. The second measurement (TSA2) was performed on the 4th day of ETI in the study group and just before extubation in the control group. The difference between TSA2 and TSA1 was defined as tongue edema. Also, the effect of tongue edema on the oxygen saturation levels measured at the 2nd h after extubation of the patients in the control group was investigated. Results: The tongue edema was more prevalent in the study group (p < 0.01). A significant negative correlation was found between the SpO2 levels two hours after extubation and the increase in the mean TSA values indicating tongue edema (p < 0.01). The oxygen saturations of the patients with tongue edema were 4% lower than those without tongue edema. Conclusions: Tongue edema may develop due to the long-term application of pressure of the ETI tube on the tongue and may impair oxygenation after extubation. ClinicalTrials.gov Identifier: NCT05249738.