Background. We hypothesized that previously reported contradictory results regarding the equivalence of mixed venous (Smv(O2)) and cerebral (rS(c)O(2)) oxygen saturation might be related to time delay issues and to measurement technology. In order to explore these two factors, we designed a prospective clinical study comparing Smv(O2) with relative (INVOS (R)) and absolute (Foresight (R)) rS(c)O(2) measurements. Methods. Forty-two consenting patients undergoing elective off-pump coronary artery bypass grafting were included. Two INVOS and two Foresight sensors continuously registered rS(c)O(2). Smv(O2) was measured continuously via a pulmonary artery catheter. Data were assessed by within-and between-group comparisons and correlation analysis. Results. A similar time delay of 19 (4) and 18 (4) s was found for Smv(O2) compared with rS(c)O(2) measurements by Foresight and INVOS, respectively, during haemodynamic changes. After adjusting for this time delay, the correlation between SmvO(2) and rS(c)O(2) increased from r=0.25 to 0.75 (P<0.001) for Foresight, and from r=0.28 to 0.73 (P<0.001) for INVOS. Comparison of Foresight and INVOS revealed significant differences in absolute rS(c)O(2) values (range 58-89% for Foresight and 28-95% for INVOS). Changes in rS(c)O(2) in response to acute haemodynamic alterations were significantly more pronounced with INVOS compared with Foresight (P<0.001). Conclusions. Considering the important time delay with Smv(O2), rS(c)O(2) seems to reflect more appropriately acute haemodynamic alterations. This might suggest its use as a valid alternative to invasive monitoring of tissue oxygen saturation. Relative and absolute rS(c)O(2) measurements demonstrated significant differences in measured rS(c)O(2) values and in the magnitude of rS(c)O(2) changes during haemodynamic alterations.