Sale, eight points adrift at the foot of the table, entertain the 11th-placed Exiles at Salford City Stadium.
The game comes after a difficult few days that saw Bryan Redpath removed as Sharks rugby director and appointed to a new role of head coach.
Club chief executive Steve Diamond will be in charge of team matters until the end of this season, but former Sale boss Mitchell has helped with preparations this week before returning to South Africa, where he is currently engaged in a legal dispute with the Johannesburg-based Golden Lions.
"He (Mitchell) has come as a consultant just to give a helicopter view of how we do things and how we can smarten things up," Diamond said.
"He has worked extensively with Bryan and myself, and it seems to be going well.
"Our preparations seem to be getting better, even though our results haven't changed."
Sale's latest league defeat - a 23-16 reversal at Worcester last Friday - was a seventh in succession and continued their dismal start to a Premiership season that has so far seen them collect just two losing bonus points.
The Sharks show two changes from events at Sixways, with Australian Cameron Shepherd replacing wing Tom Brady and Scotland international lock Richie Gray returning after injury instead of Kearnan Myall.
Mark Cueto, meanwhile, switches from the left to right wing and needs one try to equal the all-time Premiership career record of 75 touchdowns held by his former Sale colleague Steve Hanley.
Wing Marland Yarde has recovered from injury to return for Irish, with Samoan international Sailosi Tagicakibau switching into midfield instead of Jonathan Joseph, where he partners Guy Armitage.
Elsewhere, scrum-half Darren Allinson starts his first game of the season, while ex-Gloucester player Scott Lawson fills the hooking role and lock George Skivington is back after injury on the bench.
"Friday night will be a big test of how far we have come this season," Irish rugby director Brian Smith said.
"We played some great rugby (against Harlequins) last weekend and were disappointed not to see it through. We need to make amends tomorrow night.
"We face a difficult challenge. It will be a tough ask, but one that we are looking forward to."
Sale Sharks: 15 Nick Macleod, 14 Mark Cueto, 13 Johnny Leota, 12 Sam Tuitupou, 11 Cameron Shepherd, 10 Danny Cipriani, 9 Cillian Willis, 8 Andy Powell, 7 David Seymour (capt), 6 Richie Vernon, 5 Fraser McKenzie, 4 Richie Gray, 3 Tony Buckley, 2 Tommy Taylor, 1 Ross Harrison.
Replacements: 16 Joe Ward, 17 Eifion Lewis-Roberts, 18 Vadim Cobilas, 19 Kearnan Myall, 20 Mark Easter, 21 Dwayne Peel, 22 Rob Miller, 23 Tom Brady.
London Irish: 15 Anthony Watson, 14 Topsy Ojo, 13 Guy Armitage, 12 Sailosi Tagicakibau, 11 Marland Yarde, 10 Ian Humphreys, 9 Darren Allinson, 8 Chris Hala'ufia 7 Jamie Gibson, 6 Declan Danaher (Captain), 5 Matt Garvey, 4 Bryn Evans, 3 Halani Aulika, 2 Scott Lawson, 1 Max Lahiff.
Replacements: 16 Brian Blaney, 17 Cai Griffiths, 18 Leo Halavatau, 19 George Skivington, 20 Ofisa Treviranus, 21 Steven Shingler, 22 Shane Geraghty, 23 Jack Moates.
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