In the tritium breeding system for a fusion reactor, the addition of a large flow rate of hydrogen (H2) or deuterium (D2) to the helium purge gas is considered essential to avoid a large amount of tritium inventory. However, the tritium concentration in the hydrogen isotope mixture to be separated is reduced by two or three orders of magnitude by the addition. The effects of the drastic dilution of tritium by H2 or D2 on the isotope separation by cryogenic distillation are analyzed. The analysis is made under the conditions of the Japanese Fusion Engineering Reactor where the tritium production rate is 3 g/h. It is shown that the dilution requires a specific cascade in addition to the cascade in the mainstream fuel circulation system. The H2 addition is much more favorable than the D2 addition in terms of the cascade scale needed, tritium inventory within the cascade, and refrigeration capacity required. The dilution of tritium by H2 by two orders of magnitude requires a two-column cascade, and the tritium inventory and refrigeration capacity required are ∼8 g and 65 W, respectively. The dilution by three orders of magnitude requires a three-column cascade, and the values of the two parameters are ∼12 g and 630 W, respectively. In these cases, the tritium inventory and refrigeration capacity required for the cascade in the mainstream fuel circulation system are ∼70 g and 110 W, respectively. Thus, the dilution up to three orders of magnitude could pose no serious problem in the isotope separation.