Purpose: Cerebral oxygenation as measured by near-infrared spectroscopy (NIRS) might be useful to discriminate between physiological and pathological responses after standing up in individuals with orthostatic hypotension. This study addressed the physiological sensitivity of the cerebral oxygenation responses as measured by NIRS to different types and speeds of postural changes in healthy adults and assessed the reliability of these responses. Methods: Cerebral oxygenated hemoglobin (O 2 Hb), deoxygenated hemoglobin (HHb) and tissue saturation index (TSI) were measured bilaterally on the forehead of 15 healthy individuals (12 male, age range 18–27) using NIRS. Participants performed three repeats of sit to stand, and slow and rapid supine to stand movements. Responses were defined as the difference between mean, minimum and maximum O 2 Hb, HHb and TSI values after standing up and baseline. Test–retest, interobserver and intersensor reliabilities were addressed using intraclass correlation coefficients (ICCs). Results: The minimum O 2 Hb response was most sensitive to postural changes and showed significant differences (− 4.09 µmol/L, p < 0.001) between standing up from sitting and supine position, but not between standing up at different speeds (− 0.31 µmol/L, p = 0.70). The minimum O 2 Hb response was the most reliable parameter (ICC > 0.6). Conclusions: In healthy individuals, NIRS-based cerebral oxygenation parameters are sensitive to postural change and discriminate between standing up from supine and sitting position with minimum O 2 Hb response as the most sensitive and reliable parameter. The results underpin the potential value for future clinical use of NIRS in individuals with orthostatic hypotension.