Measuring a patients' oxygen consumption (VO2) is valuable in critical care and during anesthesia. Up to now, there has been no satisfactory equation describing the relation between the VO2, the fresh gas, and F(I)O(2) in a semi-closed circle breathing system. By adopting a "volume-weighted average concentration" approach and stepwise calculations, we have proposed an equation. We constructed a model with known simulated O(2) consumption ((SIM)VO2) to test our equation and two other previous methods (Biro's and Azami's). After 32 different laboratory scenarios, the %-error of the calculated VO2 ((CAL)VO2) from our method is -4.0 +/- 2.9%, which is significantly better than those from Azami's method (-8.8 +/- 6.2%, p < 0.01) and from Biro's method (-27.4 +/- 5.1%, p < 0.01). We also produce a Bland-Altman analysis of our (CAL)VO2 and (SIM)VO2. The 95% limits of agreement are -18.6-3.3 mL/min with a mean bias of -7.7 mL/min, which shows a good agreement. Our equation also explains the difference between F(I)O(2) and the oxygen concentration of the fresh gas in a semi-closed circle breathing system.