With Jim Hamilton and Scott Lawson both away with Scotland, Will James and Darren Dawidiuk coming into the starting XV.
The other enforced switch comes in the centres with Henry Trinder replacing the sidelined Eliota Fuimaono-Sapolu.
"They're a good side and I've a lot of respect for them," said coach Bryan Redpath.
"And for Conor (O'Shea) as well. They're a rugby playing side too. They're not a side that's boring to play against, they have some tricks up their sleeve.
"Every game we've improved. We've had our chances against them, they've just been far more clinical with the opportunities they've created.
"It's a real challenge but a good one, and one we should be looking forward to."
Jordan Turner-Hall comes straight back into the starting XV for Harlequins.
Turner-Hall appeared off the bench for England for the wins over Scotland and Italy but he has been released to play for his club.
However while Turner-Hall is free to play, Mike Brown is on the bench for England so Ross Chisholm starts at full-back.
Karl Dickson will make his 50th appearance for the club after getting the nod ahead of Danny Care at scrum-half,
In the pack there is a further three changes, with Will Skinner, Tomas Vallejos and Joe Gray handed starts.
Gloucester: 15 Jonny May, 14 Charlie Sharples, 13 Henry Trinder, 12 Mike Tindall, 11 James Simpson-Daniel, 10 Freddie Burns, 9 Rory Lawson, 8 Matt Cox 7 Akapusi Qera, 6 Tom Savage (c), 5 Alex Brown, 4 Will James, 3 Rupert Harden, 2 Darren Dawidiuk, 1 Nick Wood.
Replacements: 16 Matias Cortese, 17 Dan Murphy, 18 Shaun Knight, 19 Peter Buxton, 20 Brett Deacon, 21 Dave Lewis, 22 Ryan Mills, 23 Tom Voyce.
Harlequins: 15 Ross Chisholm, 14 Tom Williams, 13 George Lowe, 12Jordan Turner-Hall, 11 Ugo Monye, 10 Nick Evans, 9 Karl Dickson, 8 Nick Easter (c), 7 Will Skinner, 6 Tom Guest, 5 Tomas Vallejos, 4 Ollie Kohn, 3 James Johnston, 2 Joe Gray, 1 Joe Marler.
Replacements: 16 Chris Brooker, 17 Mark Lambert, 18 Tim Fairbrother, 19 Pete Browne, 20 Luke Wallace, 21 Danny Care, 22 Rory Clegg, 23 Matt Hopper.
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