Although previous studies have shown correlation between regional cerebral oxygen saturation (rScO₂) and mixed venous oxygen saturation (SvO₂), there is a lack of pragmatic information on the clinical applicability of these findings, such as tracking ability. We retrospectively analyzed continuous intraoperative recordings of rScO₂ and SvO₂ obtained from a pulmonary artery catheter and either of two near-infrared spectroscopy (NIRS) devices (INVOS 5100C, Medtronic; O3, Masimo) during off-pump cardiopulmonary bypass (OPCAB) surgery in adult patients. The ability of rScO₂ to track SvO₂ was quantitatively evaluated with 5 min interval changes transformed into relative values. The analysis included 176 h of data acquired from 48 subjects (26 and 22 subjects for INVOS and O3 dataset, respectively). The area under ROC of the left-rScO₂ for detecting change of SvO₂ ≥ 10% in INVOS and O3 datasets were 0.919 (95% CI 0.903–0.936) and 0.852 (95% CI 0.818–0.885). The concordance rates between the interval changes of left-rScO₂ and SvO₂ in INVOS and O3 datasets were 90.6% and 91.9% with 10% exclusion zone. rScO₂ can serve as a noninvasive tool for detecting changes in SvO₂ levels, a critical hemodynamic measurement.