Head coach Pat Howard sticks with the same outside backs but brings in a new half-back partnership in Paul Burke and Scott Bemand.
Gavin Hickie and Alex Moreno replace James Buckland and Julian White in the front row, with the latter on international duty with England at Croke Park.
Having been a part of two successive England Saxons Six Nations victories, Jordan Crane returns to the Tigers line-up at No.8, with Brett Deacon moving to the blindside flank and Tom Croft dropping to the bench.
"Paul Burke gets the nod at 10 this week as a reward for his performance in the win over Newcastle and also because I want to keep competition high for the position," said Howard. "Andy Goode is recovering from his hamstring injury and Ian Humphreys had a great couple of games in Europe but I want to keep the competition strong there.
"The competition is also fierce at scrum-half and Scott Bemand has had to wait to get his chance over the past couple of weeks. I have three good guys in there and I want to make sure I give them all a chance to put their case forward.
"With the internationals away, we do not have a huge number of options in the pack, but the back row is changed this week. Tom Croft is on the bench but that is not a reflection of how he played against Worcester last week. Jordan Crane had been playing well and we were also looking for a back row to play against Northampton's combinations there.
Luke Abraham has had a shoulder injury for a little while but I am happy to welcome him back into the 22 this weekend."
Tigers
15 Sam Vesty
14 Seru Rabeni
13 Dan Hipkiss
12 Ollie Smith
11 Alesana Tuilagi
10 Paul Burke
9 Scott Bemand
1 Marcos Ayerza
2 Gavin Hickie
3 Alex Moreno
4 Leo Cullen (capt)
5 Ben Kay
6 Brett Deacon
7 Shane Jennings
8 Jordan Crane
Replacements
16 James Buckland
17 Michael Holford
18 Tom Croft
19 Luke Abraham
20 Frank Murphy
21 Ian Humphreys
22 Daryl Gibson