Leinster fly-half Jonathan Sexton will play his first game of the season against the Ospreys on Friday having recovered from shoulder surgery.
Leo Cullen has made a number of changes from the XV that defeated Edinburgh with two in the backs and a further four tweaks in the pack.
Zane Kirchner continues in the number 15 jersey with Isa Nacewa captaining the side once again from the right wing. Dave Kearney is selected on the left.
In the centre Noel Reid and Garry Ringrose are named to start for the fourth game in a row, however thare are two changes in the half-backs.
Luke McGrath starts at scrum-half while Sexton starts alongside him.
In the pack there are two changes in the front-row with Cian Healy and Tadhg Furlong coming in, while Sean Cronin continues at hooker.
Mick Kearney comes into the second-row having lined out for Clontarf in the All-Ireland League last weekend to partner Devin Toner.
There is one final change in the pack as Josh van der Flier starts at open side flanker with Jordi Muprhy and Jamie Heaslip completing the line-up.
There is also a welcome return from injury for Rhys Ruddock who is involved in a matchday squad for the first time this season from the bench.
For the Ospreys there will be landmark games for Alun Wyn Jones, who makes his 200th appearance for the region, and Jeff Hassler, who hits game number 50 on Friday.
Rhys Webb and Dan Biggar form an all-international half-back combination as Sam Davies lines up at full-back in a strong backline.
Eli Walker was unavailable for selection to be with his partner who is due to give birth, with head coach Steve Tandy excited about the game.
"There's no bigger challenge in the PRO12 than going to the RDS to face a fully loaded Leinster team so we know we're in for a tough evening," he said as his side sits top of the table going into Round 4.
"We've made a positive start to the season but we know it doesn't count for anything at this point. We have to go up a few levels now with Ulster away and then the Blues at the Liberty coming up after this weekend. We'll definitely have a better grasp of where we are at in a few weeks time.
"It's not been perfect, there are 'work ons' that have kept us grounded, but we know we are heading in the right direction. Friday is going to be our toughest test yet, against a side that we've enjoyed some memorable battles with, and we are really looking forward to it. Our focus will be on our performance, the areas that we can control. If we do what we have to do, performance follows."
Form: Leinster are unbeaten in their last 16 Guinness PRO12 home games since the Dragons' 16-14 victory at the RDS Arena in February 2015. Ospreys became the first side to record maximum league points after three rounds of the Guinness PRO12 with their 64-10 demolition of Benetton Treviso on Saturday. The Welshmen have now recorded a try bonus point in each of their last seven matches in the PRO12, including their defeat at home to Ulster in round 22. Leinster’s only defeat to the Ospreys in their last nine encounters in all competitions was 19-25 at Liberty Stadium in the Guinness PRO12 in April 2014. Ospreys' most recent victory at the RDS Arena came in the 2012 PRO12 final.
Leinster: 15 Zane Kirchner, 14 Isa Nacewa (c), 13 Garry Ringrose, 12 Noel Reid, 11 Dave Kearney, 10 Johnny Sexton, 9 Luke McGrath, 8 Jamie Heaslip, 7 Josh van der Flier, 6 Jordi Murphy, 5 Mick Kearney, 4 Devin Toner, 3 Tadhg Furlong, 2 Sean Cronin, 1 Cian Healy
Replacements: 16 James Tracy, 17 Jack McGrath, 18 Mike Ross, 19 Ross Molony, 20 Rhys Ruddock, 21 Dan Leavy, 22 Jamison Gibson-Park, 23 Joey Carbery
Ospreys: 15 Sam Davies, 14 Jeff Hassler, 13 Ashley Beck, 12 Josh Matavesi, 11 Ben John, 10 Dan Biggar, 9 Rhys Webb, 8 Tyler Ardron, 7 Justin Tipuric, 6 James King, 5 Alun Wyn Jones (c), 4 Lloyd Ashley, 3 Dmitri Arhip, 2 Scott Baldwin, 1 Paul James
Replacements: 16 Sam Parry, 17 Nicky Smith, 18 Ma’afu Fia, 19 Bradley Davies, 20 Dan Baker, 21 Tom Habberfield, 22 Dafydd Howells, 23 Dan Evans
Date: Friday, September 23
Kick-off: 19:35 BST (18:35 GMT)
Referee: Marius Mitrea (Italy)
Assistant referees: Matteo Liperini (Italy), Stuart Gaffikin (Ireland)
TMO: Carlo Damasco (Italy)