Wales international Cuthbert replaces Harry Robinson on the wing for the trip to Salford City Stadium.
The Blues, who reached the quarter-finals last season, have also made four changes up front with Sam Warburton, Marc Breeze, Bradley Davies and Tafa'ao Filise all included.
Sale, yet to win in the Aviva Premiership this season, have named youngsters Will Addison, Nathan Fowles, Mark Jennings and Tommy Taylor in their starting XV.
Addison switches to outside centre and Fowles teams up at half-back with Nick Macleod, following two appearances off the bench against Bath and Leicester Tigers.
Jennings will make his senior debut on the right wing, while Taylor is at hooker in an unchanged pack.
Both sides are looking to turn around recent poor results; Sale have lost all six of their matches this season, while Cardiff suffered back-to-back home defeats against Ulster and Glasgow in their most recent outings.
Sale: 15 Rob Miller, 14 Mark Jennings, 13 Will Addison, 12 Sam Tuitupou, 11 Mark Cueto, 10 Nick Macleod, 9 Nathan Fowles, 8 Andy Powell, 7 David Seymour (c), 6 Richie Vernon, 5 Fraser McKenzie, 4 Richie Gray, 3 Tony Buckley, 2 Tommy Taylor, 1 Eifion Lewis-Roberts.
Replacements: 16 Joe Ward, 17 Ross Harrison, 18 Vadim Cobilas, 19 Kearnan Myall, 20 James Gaskell, 21 Cillian Willis, 22 Danny Cipriani, 23 Johnny Leota.
Cardiff Blues: 15 Leigh Halfpenny, 14 Alex Cuthbert, 13 Gavin Evans, 12 Jamie Roberts, 11 Tom James, 10 Ceri Sweeney, 9 Lloyd Williams, 8 Andries Pretorius (c), 7 Sam Warburton, 6 Josh Navidi, 5 Lou Reed, 4 Bradley Davies, 3 Benoit Bourrust, 2 Marc Breeze, 1 Tafa'ao Filise. Replacements: 16 Andi Kyriacou, 17 Nathan Trevett, 18 Scott Andrews, 19 James Down, 20 Robin Copeland, 21 Lewis Jones, 22 Gareth Davies, 23 Dan Fish.
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