AbstractWe investigated the proteins of erythrocytes from stem cell transplantation patients and found decreased expression of band3 and C‐terminal‐truncated peroxiredoxin 2 (PRDX2) only during severe graft‐versus‐host disease (GVHD), using time‐of‐flight mass spectrometry (TOF‐MS) analysis and Western blotting. During the same period, PRDX2 dimerization and calpain‐1 activation were observed, indicating severe oxidative stress. We also found a putative cleavage site for calpain‐1 in the C‐terminal‐truncated site of PRDX2. Decreased band3 expression impairs the plasticity and stability of erythrocytes, and C‐terminal‐truncated PRDX2 induces irreversible dysfunction of antioxidant activity. These effects may exacerbate microcirculation disorders and the progression of organ dysfunction.