Carbon dioxide transfer rate (CTR) is an important performance characteristic of a hollow fiber membrane oxygenator (HFMO), which is used as an artificial lung in clinical practices. In vitro measurement of CTR through HFMOs is challenging specifically in investigations with natural blood. In this study, a straightforward and applicable method is presented in order to simulate blood CO 2 exchange through HFMOs and consequently calculate the corresponding CTR. The method is based on CO 2 dissociation in deionized water resulting in pH drop of the aqueous solution. The results of proposed method are then validated comparing with in vitro investigations using native porcine blood (NPB) in two types of commercially available HFMOs. Moreover, an innovative relationship between effective membrane surface area, blood retention time, and mixing ratio of CO 2 and N 2 gases in pH drop experiment is introduced in order to simulate the CTR of complicated NPB investigations. The results reveal a good agreement between pH-based calculated CTRs and those investigated conventionally using NPB. This method would be principally applicable not only for other cylindrical HFMOs but also for other configurations of hollow fiber membrane contactors.