The former England and Lions international has spent his entire career at Bath, with director of rugby Gary Gold hailing the achievement.
"To make 250 appearances for a club is a great achievement in professional rugby, and it's a testament both to Lee's ability and his attitude as a player that he has reached it, as well as appearing for his country and the Lions," said Gold.
Francois Louw's call-up to the South Africa squad means there is a rejigged back-row for the clash, with Simon Taylor returning on the blindside, Carl Fearns switching to openside and Ben Skirving starting at No.8.
Chris Bell and Tom Palmer have been named in the Wasps starting XV following the agonising 42-40 loss to Harlequins.
Bell, who has been sidelined since November with an Achilles problem, replaces Andrea Masi, while Palmer starts ahead of the benched Joe Launchbury.
There is an additional switch on the bench, with Charlie Davies providing scrum-half cover.
Bath: 15 Nick Abendanon, 14 Tom Biggs, 13 Dan Hipkiss, 12 Matt Banahan, 11 Kyle Eastmond, 10 Olly Barkley, 9 Michael Claassens, 8 Ben Skirving, 7 Carl Fearns, 6 Simon Taylor, 5 Dominic Day, 4 Stuart Hooper (c), 3 David Wilson, 2 Lee Mears, 1 Nathan Catt.Replacements: 16 Ross Batty, 17 Paul James, 18 Kane Palma-Newport, 19 Dave Attwood, 20 Josh Ovens, 21 Mark McMillan, 22 Ollie Devoto, 23 Jack Cuthbert.
London Wasps: 15 Hugo Southwell (c), 14 Christian Wade, 13 Elliot Daly, 12 Chris Bell, 11 Tom Varndell, 10 Nick Robinson, 9 Joe Simpson, 8 Billy Vunipola, 7 Jonathan Poff, 6 James Haskell, 5 Tom Palmer, 4 Marco Wentzel, 3 Fabio Staibano, 2 Tom Lindsay, 1 Tim Payne.Replacements: 16 T Rhys Thomas, 17 Simon McIntyre, 18 Zak Taulafo, 19 Joe Launchbury, 20 Ashley Johnson, 21 Charlie Davies, 22 Tommy Bell, 23 Chris Mayor.
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