Danny Wilson has made four changes to his Cardiff Blues side ahead of the Judgement Day IV clash with the Ospreys at Principality Stadium.
The Blues take on their great rivals in the first match of a double-header and must win to keep alive their hopes of a top six finish in the PRO12.
Both Lloyd Williams and Rhys Patchell have failed to recover from the injuries they picked up in the 28-8 victory over Dragons and are replaced by Lewis Jones and Aled Summerhill.
Up front Matthew Rees gets the nod ahead of Kristian Dacey while Josh Navidi comes in at number eight, with Josh Turnbull moving into second-row and Jarrad Hoeata dropping to the bench.
"Unfortunately Lloyd and Rhys have not recovered in time for this weekend but we have had a good week of training and are looking forward to Judgement Day," said Wilson.
"It should be a really exciting game at the Principality Stadium in front of more than 65,000 fans."
Wales' capital region must beat the Ospreys and then Edinburgh in the final round of the PRO12 season to give themselves the best chance of a top six finish.
That would secure a spot in the top tier Champions Cup and while they have lost their last nine encounters against the Ospreys, Wilson is optimistic.
Wilson added: "It's another derby and we have prepared for every one previously as a massive fixture and are not looking any further.
"We have won four from five derbies so far this season and it would be great to make it five from six with a win against the Ospreys."
Meanwhile, centre Josh Matavesi will make his 50th Ospreys appearance if he comes off the bench on Saturday.
Rhys Webb captains the side from scrum-half alongside Dan Biggar, with Owen Watkin and Jonathan Spratt the midfield combination.
Wales international Dan Lydiate will start the game at number eight and is joined in the back-row by James King and Olly Cracknell.
Form: Cardiff Blues and Ospreys are chasing to become the second highest placed Welsh side. Cardiff Blues have won their last four Guinness PRO12 matches and have not won five in a row in the tournament since 2010. The Blues only previous win on 'Judgement Day' came on the only occasion they have not faced Ospreys – beating Scarlets in 2014. Ospreys have won their last two Guinness PRO12 matches since their 16-25 reversal at home to Scarlets in round 18. Ospreys have made five previous appearances at Principality Stadium in all tournaments, and won them all. Ospreys have won their last nine encounters with the Blues in the Guinness PRO12 since the two sides played out a 21-all draw at Liberty Stadium in April 2011.
Cardiff Blues: 15 Dan Fish, 14 Aled Summerhill, 13 Garyn Smith, 12 Rey Lee-Lo, 11 Tom James, 10 Gareth Anscombe, 9 Lewis Jones, 8 Josh Navidi, 7 Ellis Jenkins, 6 Sam Warburton, 5 James Down, 4 Josh Turnbull, 3 Taufa'ao Filise, 2 Matthew Rees, 1 Gethin Jenkins (c)
Replacements: 16 Kristian Dacey, 17 Brad Thyer, 18 Dillon Lewis, 19 Jarrad Hoeata, 20 Manoa Vosawai, 21 Tomos Williams, 22 Jarrod Evans, 23 Gavin Evans
Ospreys: 15 Dan Evans, 14 Hanno Dirksen, 13 Jonathan Spratt, 12 Owen Watkin, 11 Ben John, 10 Dan Biggar, 9 Rhys Webb (c), 8 Dan Lydiate, 7 James King, 6 Olly Cracknell, 5 Rynier Bernardo, 4 Adam Beard, 3 Dmitri Arhip, 2 Scott Baldwin, 1 Nicky Smith
Replacements: 16 Sam Parry, 17 Gareth Thomas, 18 Aaron Jarvis, 19 Rory Thornton, 20 Sam Underhill, 21 Brendon Leonard, 22 Sam Davies, 23 Josh Matavesi
Date: Saturday, April 30
Venue: Principality Stadium, Cardiff
Kick-off: 14:30 BST (13:30 GMT)
Referee: Nigel Owens (Wales)
Assistant Referees: Leighton Hodges (Wales), Martyn Lewis (Wales)
TMO: Jon Mason (Wales)