Atomistic modeling shows that Cu-Nb and Cu-V interfaces contain high excess atomic volume due to constitutional vacancy concentrations of ~5%at. and ~0.8%at., respectively. This finding is supported by experiments demonstrating that a ~5-fold higher He concentration is required to observe He bubbles via throughfocus transmission electron microscopy at Cu-Nb interfaces than in Cu-V interfaces.Interfaces with structures tailored to minimize precipitation and growth of He bubbles may be used to design damage-resistant composites for fusion reactors.Unlike pure metals 1 , some materials contain constitutional vacancies that are thermodynamically stable at arbitrarily low temperature, for example grain boundaries (GBs) in ceramics 2 and semiconductors 3 , compounds with wide phase fields like NiAl 4 , and certain metal hydrides 5 . We use atomistic modeling to show that Cu-Nb and Cu-V interfaces contain high constitutional vacancy concentrations.Indirect experimental verification of this prediction is obtained by measuring the critical He concentration at which bubbles become detectable at these interfaces in transmission electron microscopy (TEM).