Both sides suffered losses to Newcastle Falcons and Wasps in the opening round of games, but have named a more experienced side for the derby clash at Cardiff Arms Park.
Ospreys came out on top in this clash last season, as a four second half tries sealed the Swansea-based region a 7-31 win.
Gareth Anscombe makes a welcome return for Cardiff Blues and is in line to make his first appearance of the season, having recovered from a groin injury.
The side is captained by Gethin Jenkins, who continues his comeback from injury, while Kirby Myhill, Damian Welch and Macauley Cook are further changes in the pack.
Alongside, there are two other changes made to the backline from last week’s defeat at Kingston Park, with Lewis Jones and Steven Shingler reintroduced at scrum-half and inside centre respectively.
Luke Crocker and Max Llewellyn will make their regional debuts if called upon from the bench.
Ospreys, meanwhile, are boosted by the return of Welsh international trio Rob McCusker, James Hook and Scott Baldwin to their starting line-up.
Outside half, Luke Price, is named skipper for the derby clash, with internationals Dafydd Howells, Rhodri Jones and Rory Thornton keeping their place following last week’s defeat to Wasps at Liberty Stadium.
What They Said
Richard Hodges, who takes charge of the side for the Anglo Welsh Cup campaign, is looking forward to a Friday night derby in the capital city and is excited by the mix of experience and youth included in his side.
"We have more than half an eye on Connacht next week, so we'll select what our side is there and see which players need rugby and want to integrate some of the youngsters," said Hodges.
"What you will see this weekend is two very competitive, and I predict very close, derbies. Teams will pick like-for-like.
"We like the look of our side. It's a real good mix of experience and youth. There are some boys who have had a long time out with injury who will be coming back for some capped game-time, and more boys who will be making their debut for the region, so it will be a good day for them as well.
"We're at home, in a Welsh derby, with a strong spine to our side and we're excited."
Steven Shingler insists that the Anglo-Welsh Cup derby clash against Ospreys is a perfect opportunity to build momentum ahead of a potential season-defining block of Guinness PRO14 and European fixtures.
"There will be a few changes, and I think last year was similar in that we had a two-week Anglo-Welsh Cup break and then played Connacht so we might play a bit more well-known players in this game," said Shingler.
"We had a tough start to the season with the three Irish teams away, but we've built up a bit of form and only lost two in the last seven games.
"The plan is to get a good win against the Ospreys, going into Connacht, which is what the doctor would order, and that's what we'll try to achieve.
"In these derbies, you come up against players you've seen playing just down the motorway. The derbies around Christmas are the big ones, but this isn't far off.
"Playing against the Ospreys and being a Llanelli boy, it's always a big game, and Cardiff Blues have a lot of history against them.
"Last time we played against them was at the Principality Stadium, and they'll want to get one back on us.
"We're playing Ospreys at home, and we don't often play them at the Arms Park, because of Judgement Day, so we'll be looking to put a marker down before we go down to them around Christmas-time."
Cardiff Blues: Rhun Williams; Harri Millard, Owen Lane, Steven Shingler, Tom James; Gareth Anscombe, Lewis Jones; Gethin Jenkins (C), Kirby Myhill, Anton Peikrishvili, George Earle, Damian Welch, Macauley Cook, Sion Bennett, Shane Lewis-Hughes
Replacements: Ethan Lewis, Rhys Carre, Keiron Assiratti, Ben Murphy, Luke Crocker, Dane Blacker, Ben Thomas, Max Llewellyn
Ospreys: James Hook; Dafydd Howells, Tom Williams, Kieran Williams, Jay Baker; Luke Price (C), Reuben Morgan-Williams; Gareth Thomas, Scott Baldwin, Rhodri Jones, James Ratti, Rory Thornton, Guy Mercer, Will Jones, Rob McCusker
Replacements: Ifan Phillips, Rowan Jenkins, Alex Jeffries, Bradley Davies, Morgan Morris, Matthew Aubrey, Sam Davies, Rhys Williams