Michael Bradley is linking Saturday's clash with the final pool game the following Friday at home to French side Dax - Connacht need to win at least one of these games to book a quarter-final spot.
"We are taking the two games as a pair and will be using our full squad over the two games," he said.
"We have made a lot of changes as the same team, more or less, has played the last three matches against Munster, Leinster and the Scarlets in 13 days and could not be expected to play five games in-a-row.
"We need a win and probably a bonus point from these two games and that should be enough for us to qualify."
Connacht look to be aiming for one of the runners-up spots as London Irish, currently six points ahead, would need to lose to both Connacht and Italian side Rovigo to be overtaken.
With regular skipper John Muldoon on the bench, former London Irish hooker Adrian Flavin will captain the Connacht side on Saturday.
CONNACHT (v London Irish): Daniel Riordan; Fionn Carr, John Hearty, Mel Deane, Troy Nathan; Andy Dunne, Kieran Campbell; John Lyne, Adrian Flavin (capt), Ronan Loughney, Michael Swift, Andrew Farley, Andrew Browne, David Gannon, Colm Rigney.
Replacements: Joey Merrigan, Brian McGovern, Mike McCarthy, John Muldoon, Conor O'Loughlin, Ian Keatley, Mike Roberts.