The clubs meet at Sandy Park on Saturday (kick-off 3pm) with Exeter knowing victory would guarantee a last-eight spot.
And such an achievement would provide further evidence of the Chiefs' remarkable rise under Baxter which currently sees them mixing it at the business end on domestic and European fronts.
Exeter, beaten 15-12 in Perpignan two months ago, hold a one-point advantage in Pool Four over this weekend's opponents.
"I think it will be pretty special - one of the biggest fixtures we've staged as a club," Baxter said.
"We have got a big 80 minutes to get through, but we know we can attack the game and look to get something out of it. If we win, we top the group, and that is a fantastic position to be in.
"If we can keep progressing in Europe, that would be great. We are going into the last game with something to play for, so let's go for it.
"Perpignan are one of the biggest clubs in Europe. They may not be on form this season, but they could field a side with five or six current internationals and a British Lion, so there is a lot of strength there.
"If we win, we get a quarter-final, and that would be a fantastic achievement for the players."
Baxter has brought back his big guns following an easy 50-10 victory at Cavalieri Prato last time out.
Chiefs will be bolstered at half-back with the returns of Haydn Thomas and Ignacio Mieres while Luke Arscott has been named at No.15, with Gonzalo Camacho restoring his position on the right wing.
Jason Shoemark and Nick Sestaret also return in midfield and the pack sees changes too, with Richard Baxter and James Scaybrook back in the starting line-up.
Meanwhile, Perpignan's Wales international James Hook starts at fly-half with Gavin Hume set to join David Marty in midfield.
Perry Freshwater will be back in the front-row following his absence from the Dragons game last week while Romain Bezian completes the pack as he returns at No 8.
Newport-Gwent Dragons host Cavalieri in the other game in the group.
Exeter: Arscott, Camacho, Sestaret, Shoemark, Jess, Mieres, Thomas, Sturgess, Clark, Andress, Hayes, Muldowney, Johnson, Scaysbrook, Baxter.
Replacements: Alcott, Tui, Mitchell, White, Phillips, Barrett, Steenson, Dollman.
Perpignan: Michel, Sid, Marty, Hume, Plante, Hook, Mele, Freshwater, Geli, Bourrust, Taofifenua, Watchou, Britz, Perez, Bezian.
Replacements: Tincu, Schuster, Pulu, Olibeau, Guirado, Cazenave, Laharrague, Porical.
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