Leicester Tigers will welcome back internationals Toby Flood, Ben Youngs and Manu Tuilagi for Saturday's Aviva Premiership fixture against Newcastle.
All three will make their first appearances of the season in this week's Round Three fixture.
Second-rower Graham Kitchener also returns from injury for his first game of the season and there is a Tigers debut for new signings Jamie Gibson in the back-row and American international full-back Blaine Scully.
Another new face, prop Tom Bristow, is selected among the replacements alongside British and Irish Lions trio Tom Youngs, Dan Cole and Geoff Parling.
Meanwhile, Rory Clegg starts at fly-half for Newcastle for Saturday's clash with the reigning champions.
Clegg, who kicked the winning points in last week's 15-14 victory at Sale Sharks, partners Warren Fury at the heart of the Falcons' backline, while centre Danny Barnes misses out with an elbow injury with potent runner James Fitzpatrick coming in at inside centre.
Matt Thompson drops to the bench to make wake way for Rob Vickers at hooker, and former Leicester man Kieran Brookes replaces Oliver Tomaszczyk at tighthead, who is ruled out through illness.
Carlo del Fava gets the nod at second-row while Mark Wilson and Chris York round off the changes in the back-row.
Gloucester have handed 20-year-old lock Elliott Stooke his first league start for this weekend's clash with Northampton Saints.
The England U20 international has impressed the Gloucester coaching staff greatly in recent months and will partner skipper Tom Savage.
The only other changes to the side that started at Saracens last weekend see Dan Murphy start in place of the suspended Nick Wood at loosehead prop, and Jimmy Cowan get the nod at scrum-half in place of Tavis Knoyle.
Meanwhile, amongst the replacements, having come through the A League game at Sale on Monday evening, Shaun Knight and Jonny May are both named in the matchday squad for the first time.
Northampton have handed wing Jamie Elliott his first Premiership start of the season. The same goes for prop Alex Waller, who replaces a rested Alex Corbisiero, while in the back-row Sam Dickinson returns to the No 8 shirt.
Ken Pisi and Courtney Lawes start on the bench, as does prop Ethan Waller, who started Monday's 'A' League win over Worcester.
Elsewhere, London Irish have made three changes to their starting XV for their meeting with Exeter Chiefs at the Madejski Stadium.
Fergus Mulchrone will partner Eamonn Sheridan in the centre with Declan Danaher and Bryn Evans joining Ofisa Treviranus in the back row. Tomás O'Leary will continue as captain.
Former Dragons lock Ian Nimmo has joined the Exiles as cover for George Skivington and Kieran Low and has been named on the bench.