Rob Baxter's men entertain the French heavyweights at Sandy Park, while Scarlets meet Leinster, Harlequins go to Connacht and Saracens take on Racing Metro.
Three years ago this weekend, the Chiefs were preparing for a Championship game against Rotherham.
But on Saturday, Exeter make their home Heineken Cup debut, tackling one of the tournament's most star-studded teams seven days after they lost just 9-6 to European champions Leinster in Dublin.
"All week we've talked about being the team that attacks, being the team that has the ball and seeing what we can get out of the game," head coach Baxter said.
"Certainly, we are going to attack the game, look to score tries and see what comes from it.
"The major danger playing them (Clermont) is that you can't afford to switch off.
"If, at any stage, you have a loose ball or you make a loose decision, they have a counter-attacking back three that can really hurt you.
"Obviously, we know they are a very good side who can keep constant pressure on you, but sometimes you can deal with that as a team because you know it's coming.
"It is when a team can hit you from anywhere out of the blue - that is what makes them dangerous."
Baxter admitted there were mixed emotions in the Exeter camp following their narrow defeat against Leinster.
"We were disappointed with the end result, but at the same time there was also an element of relief and an element of pleasure in going there and doing a pretty good job," he added.
"Like with any team, you are always going to be disappointed when you lose a game by three points. That said, we've managed to switch our focus quickly on to this next game because in some ways this is a much bigger challenge for us.
"It is no longer our first Heineken Cup game, and it's not away to the champions. Now, we have to show some consistency against a very good side - and we have to do it at home."
Baxter has made a solitary change from the Leinster game, handing Australian recruit Dean Mumm his first European start in the second-row, where he replaces James Hanks.
The Scarlets, crushed 49-16 by Clermont last Saturday, realise their hopes of progressing from Pool Five will effectively be over if they fail to topple Leinster on home soil.
And Scarlets head coach Simon Easterby knows that his former Ireland team-mate Brian O'Driscoll remains a talismanic figure within the defending champions' ranks.
"He is very important," Easterby said.
"He's not getting any younger, but he's certainly not getting any poorer in terms of his attitude and the way he plays the game.
"He still has a real appetite, he is competitive and is someone they look to lead by example. He will have a huge influence on their game."
English champions Harlequins will take a sizeable stride toward this season's quarter-finals if they beat Connacht in Galway, but recent tournament history underlines it is not a trip they can take lightly.
Their quarter-final hopes last season were destroyed by a 9-8 loss to Connacht on the final weekend of pool stage games. Had they won, Quins would have progressed.
"We know that we face a massive challenge when we go to Galway," Quins rugby director Conor O'Shea said. "Last season is etched in our memory and we are looking forward to getting over there."
O'Shea has made two enforced changes after a resounding win against Biarritz last time out. Ankle injuries sideline fly-half Nick Evans and wing Ugo Monye, with Ben Botica and Sam Smith their respective deputies.
Finally, Saracens host Pool One rivals Racing Metro in Brussels, when the Stade Roi Baudouin will stage a fixture between the group's two unbeaten teams.
In-form Charlie Hodgson retains Saracens' number 10 shirt, but Owen Farrell also starts, featuring at outside centre, while Chris Wyles makes his 100th first team appearance and scrum-half Neil de Kock replaces Richard Wigglesworth.
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