Jonathan Thomas returns to action after seven months out through a groin injury, and is joined among the replacements by British & Irish Lion Tommy Bowe, who will make his first appearance of the season if he comes on from the bench.
Sonny Parker comes into the squad to replace Jonathan Spratt, who has shown signs of fatigue in training this week and has been rested. He is expected to train as normal over the coming week and will be available for selection next weekend.
Ospreys coach Jonathan Humphreys commented: "We welcome back Jonathan Thomas after a lengthy lay-off and it's great to see him back again, he's had a pretty frustrating time of it but he's on the comeback trail which is great news. Likewise, with Tommy returning to action after the Lions tour, it's good to see the options available to us as coaches increasing.
"We're pretty satisfied with the result in Connacht last week, to come away from what is a difficult place with a win. It could have been far worse, there were some surprising results in the first week. It was our intention to get off to a positive start and we did that. There's still a lot for us to work on, which is quite pleasing really, we don't want to be hitting the ground at 100 per cent, we are building into it and as the season progresses we'll pick up the percentages as we go.
"We've looked at the video of last weekend's game, we've worked hard to improve in certain areas, and I'd expect to see us stepping up a level on Saturday evening. We want to go out on Saturday and send the right messages out to our supporters, in terms of what we want to achieve this season. We're very excited about coming back for the start of the season and it'll be great to see a big crowd waiting for us.
"As long as our mentality is right, as long as we show the pride I expect in the performance for the first home game and set the standards, we'll be alright and it will set us off in good stead for the rest of the season. The rest will follow."
Ospreys: 15 Barry Davies 14 Jonny Vaughton 13 Sonny Parker 12 Andrew Bishop 11 Nikki Walker 10 James Hook 9 Mike Phillips; 1 Paul James 2 Richard Hibbard 3 Cai Griffiths 4 Ian Gough 5 Andy Lloyd 6 Jerry Collins 7 Marty Holah 8 Ryan Jones (capt)
Replacements: 16 Huw Bennett 17 Duncan Jones 18 Jonathan Thomas 19 Tom Smith 20 Jamie Nutbrown 21 Dan Biggar 22 Tommy Bowe
Wales reached their first semi-final since 2013 in the opening round of this season's HSBC World Rugby Sevens Series in Dubai. WRU TV's Graeme Gillespie recaps on what proved to be an eventful tournament
Wales and Ospreys back row James King, who came through the North Wales age grade system, nominated North Wales Regional Community Rugby Manager Marc Roberts, in the WRU's 'Diolch' initiative where squad players thanked those who played a part in their rise to the top.
Beating Merthyr has boosted Carmarthen Quins hopes of reaching a top eight spot in the Principality Premiership. Quins captain Haydn Pugh is delighted with his team's progress and is determined that everyone from the Under 6s through to the senior team, enjoys the ride.
When the Wales squad were asked to nominate individuals who played a big part in their early playing days, Wales and Dragons full back and wing Hallam Amos thought of his former Monmouth School rugby coach John Bevan.
Sam Cross and Luke Treharne have been named as co-captains of the Wales Sevens side as head coach Gareth Williams names his 12-man squad to play in the first leg of the HSBC World Series in Dubai next weekend.
Bedwas head coach Steve Law and players Nicky Griffiths and Alun Rees extol the virtues of the close knit club as they prepare to host third place RGC 1404 - who are one place head of them on the Principality Premiership points table - on Saturday.
Many of the Wales squad have said Diolch (thank you) to someone who played an important part in their early playing days by nominating them to be invited to the Wales v South Africa match. One person, Gowerton Comprehensive geography teacher Mr Dean Mason was nominated by two of his former pupils, Dan Biggar and Sam Davies.
The second WRU disability rugby pilot has been delivered, this time in Caerphilly schools, culminating in a festival at the Caerphilly Centre of Sporting Excellence, Ystrad Mynach tomorrow. Plans are in place to set up a Disability Rugby Club in Newbridge to provide long-term playing opportunities.
WRU TV: Hear from inside the Wales camp as Neil Jenkins discusses this weekend's clash with South Africa and how the squad are looking to put in a strong performance to round of the 2016 Under Armour Series