Background: After ischemic stroke, there is no general consensus on the optimal position for the head of patients in the acute phase. This observational study aimed to measure the variations in cortical oxygenation using noninvasive functional near-infrared spectroscopy (fNIRS) at different degrees of head positioning on a bed. Methods: Consecutive ischemic stroke patients aged 18 years or older with anterior circulation ischemic stroke within 48 h of symptom onset who could safely assume different positions on a bed were included. A 48-channel fNIRS system was placed in the bilateral sensorimotor cortex. Then, the bed of each patient was moved into four consecutive positions: (1) seated (90° angle between the head and bed surface); (2) lying at 30°; (3) seated again (90°); and (4) lying flat (0°). Each position was maintained for 90 s; the test was conducted 48 h after stroke onset and after 5 ± 1 days. The variations in oxygenated hemoglobin in the global brain surface and for each hemisphere were recorded and compared. Results: Twenty-one patients were included (males, n = 11; age, 79 ± 9 years; ASPECTS, 8 ± 2). When evaluating the affected side, the median oxygenation was significantly greater in the lying-flat (0°) and 30° positions than in the 90° position (p < 0.001 for both comparisons). No significant differences between the supine position and the 30° position were found, although oxygenation was slightly lower in the 30° position than in the supine position (p = 0.063). No differences were observed when comparing recanalized and nonrecanalized patients separately or according to stroke severity. The evaluation conducted 5 days after the stroke confirmed the previous data, with a significant difference in oxygenation at 0° and 30° compared to 90°. Conclusions: This preliminary study suggested that there are no substantial differences in brain oxygenation between the lying-flat head position and the 30° laying position.