Sam Simmonds, Stuart Hogg, Henry Slade and Luke Cowan-Dickie all return as Exeter make sweeping changes against Lyon in the Heineken Champions Cup last 16.
Fly-half Joe Simmonds and second-row pair Jonny Hill and Jonny Gray are also included in the starting XV.
Wing Olly Woodburn is the only survivor from the line-up that lost to Gloucester last time out.
France wing Noa Nakaitaci and Australia second row Izack Rodda start for Lyon.
The visitors are sixth in their domestic league, but have won their past three games including a win over Top 14 leaders Toulouse at the end of February.
Defending champions Exeter recorded four wins over French sides on their way to the trophy last season, beating La Rochelle twice in the pool stage, Toulouse in the semi-final and Racing 92 in the final.
The winners will play four-time champions Leinster in the last eight, whose last-16 tie against Toulon was called off on Friday after a positive Covid-19 test in the French camp.
"It's all or nothing now," Chiefs' director of rugby Rob Baxter said. "It's knockout rugby from here on in. Yes, it's come a bit earlier than normal, but this is the kind of challenge you expect to face when you are in the Heineken Cup.
"We know Lyon will be a huge challenge, particularly as it looks as though they are one of the form teams in France right now, so we will need a huge performance again at the weekend if we stand any hope of advancing on to next week."
Match facts
Exeter Chiefs: Hogg; Woodburn, Slade, Devoto, O'Flaherty; J Simmonds, Maunder; Hepburn, Cowan-Dickie, Williams, Gray, Hill, Ewers, Vermeulen, S. Simmonds.
Replacements: Yeandle, Moon, Francis, S. Skinner, Kirsten, Townsend, H.Skinner, Whitten
Lyon: Arnold; Mignot, Barassi, Ngatai, Nakaitaci; Wisniewski, Couilloud; Devisme, Marouard, Gomez-Kodela, Lambey, Rodda, Cretin, Fainga'a, Sobela
Replacements: Ivaldi, Chiocci, Taufete'e, Guillard, Tulou, Doussain, Regard, Laporte