We demonstrate that enantiopreference in the binding of S,S over R,R astaxanthin (AXT) to albumin manifests itself only for racemic (but not enantiopure) carotenoids. The observed enantioselectivity is rationalized using chiroptical spectroscopies supported by molecular docking, molecular dynamics and quantum-chemical calculations. These methods offer a plausible explanation for the observed enantiopreference, as they reveal a unique binding mode of the (3S,3′S)-AXT form with the protein in contrast to multiple (random) possibilities for albumin binding with the (3R,3′R)-AXT, and also a higher interaction energy of the latter enantiomer with the protein.