The 2021–22 EPCR Challenge Cup was the eighth edition of the EPCR Challenge Cup, an annual second-tier rugby union competition for professional clubs.

Due to the COVID-19 pandemic, the tournament format was changed for the previous season.

A similar format remained for this season, however, the number of teams was increased from 14 to 15 and an additional six will join from the Champions Cup.

[1] The tournament commenced in December 2021, and concluded with the final on 27 May 2022 at Stade Vélodrome in Marseille, France.

Fifteen teams qualified for the 2021–22 EPCR Cup from Premiership Rugby, the Top 14 and the United Rugby Championship as a direct result of their domestic league performance having not qualified for the Heineken Champions Cup.