Despite a strong second half performance, Richard Hodges’ young side were narrowly defeated by defending champions, Leicester Tigers, at Welford Road last week.
The Blues prepare to welcome Toyota Cheetahs to Cardiff Arms Park for the first time next week, as they look to put pressure on the South Africans for a place in the end-of-season play-off.
A host of senior squad members have been recalled into the squad as Hodges makes nine changes from the side that played at Leicester.
Olly Robinson will become the first Englishman to captain Cardiff Blues, as he lines up in a strong back row alongside Josh Turnbull and Seb Davies, who is released from Wales duty for the week.
Rhys Gill, Ethan Lewis and Keiron Assiratti form a new-look front row, while Damian Welch is reintroduced into the boiler room.
Garyn Smith is one of two changes along the backline, with the centre set to make his 50th appearance as Jack Roberts is ruled out with injury.
On the other hand, wing Ryan Edwards will make his debut for the region having made a short-term loan switch to the Welsh capital from Bristol earlier in the week.
On the bench, Dan Fish makes a long-awaited return to action, with another loan signing from Bristol, scrum half Reiss Cullen, also set to make his debut.
London Irish head into the clash on the back of three consecutive victories, as they prepare for a crucial block of games in the fight for survival in the Aviva Premiership.
The Exiles makes two changes from the side that thrashed a young Wasps side by 66-7 last week.
Scotland international, Blair Cowan, is replaced by Max Northcote-Green in the number seven jersey, while South African scrum half Piet van Zyl is set to make his first start for the club, having made a try-scoring debut off the bench last week.
Joe Cokanasiga, who is part of Eddie Jones’ England squad for the NatWest 6 Nations, starts on the wing, with Rugby World Cup winner, Ben Franks, at loosehead.
What They Said
Captain Olly Robinson knows the Anglo-Welsh Cup provides both young players a chance to impress and the collective to gain momentum as a pivotal period approaches.
"It's great, I hadn't played in the Premiership before I played in the Anglo-Welsh Cup last year but it allows you to show what you can do.
"It's a good chance for young boys and everyone else to put a performance in and start building momentum back into the league.
"Welford Road is a really tough place to play as most teams in the Premiership will tell you. To go there and be in with a chance of winning is a credit but the boys were really disappointed not to win.
"It shows how well they did that they were disappointed so we are looking forward to backing it up.
"London Irish are a really good side, they've not had the season they would've wanted in the Premiership but they're coming off the back of a really good win against Wasps. To put 50-points on any Wasps side is a real achievement so we know we have to be on our mettle to be within a chance.
"It's great that sides go full strength, they are the teams you want to face and for some of the younger boys it will be the most intense game they've played in.
"That's where you want to test yourself and it's really exciting to be able to go out and see where we are as a squad."
Meanwhile, Steven Shingler is looking forward to facing his former club, as he seeks to put his hands up for selection with crucial PRO14 fixtures around the corner.
“I’m looking forward to having another opportunity on Saturday and hopefully I can force myself back into that team,” said Shingler.
“If you look at the team we’ve put out on Friday, it’s experienced and we have an added onus to carry on the home form leading into the Cheetahs game.
“We’re out of the Anglo-Welsh Cup but we’re playing for personal pride and trying to get into form.
“The Anglo-Welsh Cup is a competition for people with very different individual goals and this week has more of a senior squad.
“Last time I started a game was probably before November, so it was a long time coming but I was blowing quite hard by the end of the 80 minutes.
“London Irish are a good outfit and we all know that the Aviva Premiership is very fiercely contested.
“Coming up from the Championship, they’ve signed a lot of players and are now getting used to their systems much better than they were at the start of the year.
“They’ll be in a very similar position to us in terms of getting ready for a return to their next league game.
"I loved it down there. It was a great two years and made a lot of good friend over there.
“Many of them are actually part of the coaching set-up now so it will be good to see them again."