Shear-induced damage of Red Blood Cell (RBC) is an imminent problem to be solved for the practical application of artificial organs in extra corporeal circulation, as it often happens and affects physiological homeostasis of a patient. To design and operate artificial organs in a safe mode, many investigations have been set up to correlate shear and shear-induced cell damage. Most studies were focused on hemolysis i.e. the extreme case, however, it is important as well to obtain a clear understanding of pre-hemolytic mechanical damage. In this study, the change in deformability of RBC was measured by ektacytometry to investigate the damage of RBC caused by shear. To a small magnitude of pre-shear, there is little difference, but to a large magnitude of pre-shear, cell damage occurs and the effect of shear becomes significant depending on both the magnitude and imposed time of shearing. The threshold stress for cell damage was found to be approximately 30 Pa, which is much less than the threshold of mechanical hemolysis but is large enough to occur in vitro as in the extra corporeal circulation during open-heart surgery or artificial heart. In conclusion, it was found and suggested that the decrease of deformability can be used as an early indication of cell damage, in contrast to measuring plasma hemoglobin. As cell damage always occurs during flow in artificial organs, the results as well as the approach adopted here will be helpful in the design and operation of artificial organs.