Presepsin, which is used as a biomarker for sepsis, is thought to be removed by dialysis, but the actual removal properties of dialysis are unknown. We investigated the presepsin removal properties of continuous hemodiafiltration using the high concentration of presepsin from human plasma drained by plasma exchange. Each solution in plasma exchange was connected to a continuous hemodiafiltration blood circuit and circulated at 4 conditions. The results show that presepsin was confirmed to be removed more efficiently in hemofiltration than in hemodialysis. In addition, when using a polymethylmethacrylate hemofilter for continuous hemodiafiltration, the lowest presepsin concentration is on the filtrate side, suggesting that the main removal mechanism is adsorption. Since presepsin has a molecular weight of 13,000, its removal efficiency is high by hemofiltration as per principle. In addition, since the main adsorption principle of polymethylmethacrylate hemofilter is hydrophobic bond, presepsin is considered to be adsorbed. Since presepsin is metabolized in the kidney, it is elevated in renal failure. In this paper, we confirmed that presepsin is eliminated by continuous hemodiafiltration not only in the kidney. Depending on the timing of presepsin measurement, there is a risk of missing the diagnosis of sepsis. Kidney function and continuous hemodiafiltration should be checked when measuring presepsin.