Background: The aim of this study was to evaluate the course of hemoglobin (HGB) concentration and hematocrit (HCT) in donor blood during and after preparatory plasmaphereses (PP) without NaCl and with an infusion of 500 ml 0.9% NaCl during PP. Methods: After informed consent 32 plasma donors were studied in a crossover design. They underwent PP once without NaCl infusion and once, on a different day, with infusion of 500 ml 0.9% NaCl. HGB concentration and HCT values in donor blood were analyzed using a Sysmex KX-21N analyzer. The values of HGB concentration and HCT before PP were set to 100%. Changes in HGB concentration and HCT were calculated in percent directly after PP, and after 24 and 72 h. Results: During PP, there was a notable change in HGB concentration (11.2 ± 4.0%) and HCT (11.6 ± 3.9%) in donor blood. The difference between the 2 samples without and with NaCl was highly significant (p < 0.001). After 24 and 72 h, all differences were reduced. Conclusion: We observed significant changes in HGB concentration and HCT in donor blood during PP. We recommend a concomitant infusion of 500 ml 0.9% NaCl during PP to all donors.