This study aimed to compare optic nerve sheath diameter (ONSD) measurements obtained during hypercapnic and normocapnic periods in mechanically ventilated patients and to describe changes in ONSD in relation to ventilation-associated carbon dioxide levels. The study included sixty intubated patients admitted to the intensive care unit with a diagnosis of pneumonia and who underwent mechanical ventilation. ONSD measurements were performed during periods of hypercapnia identified during routine monitoring. After adjustment of ventilator settings, arterial blood gas analysis (ABG) was obtained one hour later, and ONSD measurements were repeated when normocapnia was achieved. The mean age of the patients was 61.6 ± 17.9 years. During the hypercapnic period, the mean ONSD (average of both eyes) was 4.88 ± 0.31 mm. Following the achievement of normocapnia, the mean ONSD decreased significantly to 4.61 ± 0.24 mm (p < 0.001). Furthermore, a significant positive correlation was found between the change (∆) in PaCO2 and the reduction in mean ONSD (r = 0.538, p < 0.001). ONSD measurements differed significantly between hypercapnic and normocapnic periods defined by PaCO₂ levels. These findings suggest that ONSD may reflect physiological responses across different ventilatory CO₂ states.