Near-infrared spectroscopy (NIRS) is a non-invasive method that reflects real-time cerebral oxygenation (rSO₂) by the use of two adhesive optodes placed on the forehead of the patient. Frontal sinuses vary anatomically and a large frontal sinus might compromise the NIRS signal since the NIRS optodes are placed at the skin surface superficial to the underlying frontal sinus. The aim of this case-series was to elucidate whether there is a difference in the obligate changes in rSO₂ during cardiac surgery between patients with a small as opposed to a large anterior-posterior distance of the frontal sinus based on magnetic resonance imaging. Two matched groups with small (n = 5) vs. large (n = 5) frontal sinus (3.2 vs. 18.1 millimeters) in this case-series showed no difference in obligate changes of rSO₂ (p = 0.54).