Mélé is named as captain for the first time in only his 15th appearance for the club following his summer arrival from Perpignan and he teams up with Ryan Lamb in an experienced half-back combination.
Other senior players in the line-up for the trip to the Twickenham Stoop include Scott Hamilton, Adam Thompstone, Matt Smith, Rob Hawkins, Steve Mafi and Thomas Waldrom.
Richard Cockerill gives Tom Bristow his first starting appearance for the club at loosehead prop, while Argentina international Pablo Matera is brought into the back row.
Italy Under-20s tighthead prop Tiziano Pasquali, who has come through the Tigers Academy, and 18-year-old flanker Will Owen, a member of the England Under-20s squad this season, are among the replacements.
Director of rugby Richard Cockerill said: “There is a good mix of senior players who need competitive game-time with the younger guys who are looking to make an impression at this level. It’s an opportunity for them all to show what they can do in a tough competitive fixture away from home.”
Tigers currently top their pool after wins over the Ospreys and Worcester Warriors in the opening two rounds.
The last match in the pool stages is against Bath Rugby at Welford Road next Friday (7.45pm). Match tickets are available now from the Tigers ticket office or book online. For matchday hospitality packages please contact the Tigers Corporate Sales team by phoning 0116 217 1215 or alternatively click here to book online.
Leicester Tigers (v Harlequins, away, Saturday 3pm)
15 Scott Hamilton
14 Blaine Scully
13 Matt Smith
12 Terrence Hepetema
11 Adam Thompstone
10 Ryan Lamb
9 David Mele (c)
1 Tom Bristow
2 Rob Hawkins
3 Fraser Balmain
4 Steve Mafi
5 Sebastian De Chaves
6 Michael Noone
7 Pablo Matera
8 Thomas Waldrom
Replacements
16 George Chuter
17 Boris Stankovich
18 Tiziano Pasquali
19 Harry Wells
20 Will Owen
21 Scott Steele
22 Owen Williams
23 Henry Purdy
Harlequins
15 Ollie Lindsay-Hague
14 Paul Sackey
13 Harry Sloan
12 Jordan Turner-Hall
11 Tom Williams
10 Ben Botica
9 Karl Dickson (c)
1 Mark Lambert
2 Joe Gray
3 Paul Doran Jones
4 George Merrick
5 Nick Kennedy
6 Joe Trayfoot
7 Maurie Fa'asavalu
8 Tom Guest
Replacements
16 Nic Mayhew
17 Darryl Marfo
18 Kyle Sinckler
19 Kieran Treadwell
20 James Chisholm
21 Sam Stuart
22 Louis Grimoldby
23 Ugo Monye
