Flying Argentine international duo Joaquin Tuculet and Lucas Amorosino make playing comebacks on the wings after spells out injured.
Rhys Patchell makes a welcome return at full back while Gareth Anscombe makes a positional change to fly half where he will form a half back partnership with Lloyd Williams who also earns a call-up.
A new-look front row trio will see Jenkins pack down alongside Kristian Dacey and Craig Mitchell, who is in line for his first league appearance for Blues since late November.
Locks Chris Dicomidis and fit-again Filo Paulo are paired in the second row while Josh Turnbull is named in the back row.
Dale McIntosh, Defence Coach at Cardiff Blues, said: "It's going to be a great spectacle and big occasion at Judgement Day III.
"The table doesn't lie and I have a lot of respect for Ospreys and the management. They are a very complete side that is well coached at the set piece and they play at a pace that is hard to control.
"We understand to get near them and compete we have to raise our game and base our game around tenacity and physicality. We also have to maintain our discipline, because that's let us down on occasion, because they have pace and a fluid game.
"The players are in the mood and they have trained well," he added. "Gethin (Jenkins) is busting for a game and we need our big players on form and supported by the rest of the boys.
"We have a number of players returning from injury and it's important we see players like Craig Mitchell back in league action as we look ahead to next season and the future."
Cardiff Blues: 15 Rhys Patchell, 14 Lucas Amorosino, 13 Tom Isaacs, 12 Garyn Smith, 11 Joaquin Tuculet, 10 Gareth Anscombe, 9 Lloyd Williams; 1 Gethin Jenkins (c), 2 Kristian Dacey, 3 Craig Mitchell, 4 Chris Dicomidis, 5 Filo Paulo, 6 Josh Turnbull, 7 Sam Warburton, 8 Josh Navidi
Replacements: 16 Matthew Rees, 17 Sam Hobbs, 18 Scott Andrews, 19 Jarrad Hoeata, 20 Macauley Cook, 21 Lewis Jones, 22 Gareth Davies, 23 Dan Fish
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