Soluble ABO blood group substance (SAS) in fresh-frozen plasma (FFP) and its cognate alloantibody titer reduction capacity (TRC) are not considered when prescribing this product for plasma exchange (PEX) therapy of ABO incompatible transplant recipients. SAS was quantified in 250 single FFPs using ELISA. Total and IgG class-specific anti-A TRCs of FFPs were measured using a microhemagglutination inhibition assay. SAS level depended not only on the A subtype (p < 0.0001) and the Secretor status (p < 0.0001), but also on the expression of ALe(b) in A1 secretors (p < 0.0001). The variation was as great as 137.6 arbitrary units (aU) for 14 A1 Le(a-b-) secretors and 1.2 aU for 6 A2 non-secretors. Homozygous expression of the A1, A2 and Secretor alleles did not increase SAS levels. Only total anti-A TRC, but not IgG class-specific TRC depended on the detected SAS level (r = 0.566, p = 0.0003).