Exeter will guarantee top place in the Premiership if they defeat Harlequins and Saracens fail to beat Wasps.
Rob Baxter makes eight changes to the side that lost at home to Wasps a fortnight ago, with backs Jack Nowell and Santiago Cordero both out and six among the forwards.
Quins have two changes in their side after losing at Clermont Auvergne.
Francis Saili replaces Ben Tapuai in midfield, while Stan South comes in for Ben Glynn in the second row.
Quins could make themselves favourites to clinch the final play-off place if they can inflict a rare second successive home defeat on Exeter.
Phil Dollman and Tom O'Flaherty replace Cordero and Nowell at full-back and wing respectively for the home side, with Argentina back Cordero a doubt for the rest of the season after going off early against Wasps.
An all-new front row sees England props Alec Hepburn and Harry Williams pack down alongside skipper Jack Yeandle, while Dave Dennis and Jonny Hill return to the second row and Sean Lonsdale comes in for Don Armand at flanker.
Sam Hill will play his 100th game for Exeter if he features from the bench.
Exeter director of rugby Rob Baxter told BBC Sport:
"The reality is it doesn't matter how many points you collect, it's about getting that home semi-final.
"We've got that, we now have to make sure we prepare ourselves as well as we can for a semi-final and potentially a final, but there's a way of doing that, and the way of doing that is you prepare well today and you prepare flat out for a very tough game which is what we're going to have this weekend against Harlequins.
"There is a reality that we also let ourselves down a week after cementing the home semi-final place with our performance here against Wasps where without doubt we took our foot off the pedal a little bit."
Harlequins director of rugby Paul Gustard told the club website:
"This weekend's match is not only a great opportunity to build on last week's energy and effort but also for us to keep our challenge for the title.
"We had a strong game against the Chiefs at The Stoop earlier in the season and we must again be at our best if we are to defeat them.
"They are a formidable team with plenty of attacking threat and endeavour, combined with a strong set-piece which, allied to their passionate support, means they are a dangerous opponent."
Exeter: Dollman; O'Flaherty, Slade, Devoto, Woodburn; Simmonds, White; Hepburn, Yeandle (capt), Williams, Dennis, Hill, Ewers, Lonsdale, Kvesic
Replacements: Taione, Moon, Francis, Atkins, Capstick, Maunder, Steenson Hill
Harlequins: Brown; Walker, Alofa, Saili, Chisholm; Smith, Hidalgo-Clyne; Marler, Buchanan, Sinckler, Symons, South, Clifford, Robshaw (capt), Dombrandt
Replacements: Elia, Auterac, Swainston, Merrick, Kunatani. Saunders, Lang, Ibitoye
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