We applied our proposed continuous blood viscosity monitoring system for cardiopulmonary bypass to an experimental model that introduced echinocytes, and we confirm the viscosity change detection due to red blood cell (RBC) deformability decline. For the in vitro experiment, a test circuit including an oxygenator and a controlled bovine blood sample with excessive alkalemia to induce the echinocyte were prepared, and a perfusion experiment was performed. During the experiment, the anticoagulated bovine blood sample maintained a hematocrit of approximately 22%, temperature of 37°C, and more than 800 s of the activated clotting time. The estimated viscosity obtained from the proposed system was 2.10 mPas at the beginning of the experiment and 3.58 mPas at the end of the experiment, and it increased 1.48 mPas during the experiment. According to the scanning electron micrographs of blood samples, the echinocytes with multiple spicules at the beginning of the experiment and distorted spherical RBCs including the echinocytes with multiple spicules at the end of experiment were observed. We conclude that the system may be helpful for clinical perfusion management, because it detected the presence of echinocytes as the blood viscosity in an oxygenator flow pass increased.