Regional cerebral oxygen saturation (rSo2) obtained from near-infrared spectroscopy (NIRS) provides valuable information during cardiac surgery. The rSo2 is calculated from the proportion of oxygenated to total hemoglobin in the cerebral vasculature. Root O3 cerebral oximetry (Masimo) allows for individual identification of changes in total (ΔcHbi), oxygenated (Δo2Hbi), and deoxygenated (ΔHHbi) hemoglobin spectral absorptions. Variations in these parameters from baseline help identify the underlying mechanisms of cerebral desaturation. This case series represents the first preliminary description of Δo2Hbi, ΔHHbi, and ΔcHbi variations in 10 cardiac surgical settings. Hemoglobin spectral absorption changes can be classified according to 3 distinct variations of cerebral desaturation. Reduced cerebral oxygen content or increased cerebral metabolism without major blood flow changes is reflected by decreased Δo2Hbi, unchanged ΔcHbi, and increased ΔHHbi Reduced cerebral arterial blood flow is suggested by decreased Δo2Hbi and ΔcHbi, with variable ΔHHbi. Finally, acute cerebral congestion may be suspected with increased ΔHHbi and ΔcHbi with unchanged Δo2Hbi. Cerebral desaturation can also result from mixed mechanisms reflected by variable combination of those 3 patterns. Normal cerebral saturation can occur, where reduced cerebral oxygen content such as anemia is balanced by a reduction in cerebral oxygen consumption such as during hypothermia. A summative algorithm using rSo2, Δo2Hbi, ΔHHbi, and ΔcHbi is proposed. Further explorations involving more patients should be performed to establish the potential role and limitations of monitoring hemoglobin spectral absorption signals.