Pretorius is one of four changes for Blues as Director of Rugby Phil Davies looks to build on the Heineken Cup double win over Glasgow Warriors.
Centre Dafydd Hewitt is also handed a recall, with Rhys Patchell missing the game through injury, while the return of Pretorius sees Macauley Cook move to lock to partner Filo Paulo.
Prop Benoit Bourrust is named in the front row alongside hooker Kristian Dacey and skipper Sam Hobbs.
Rhys Williams, Scott Andrews, Josh Navidi and Gavin Evans are all named amongst the replacements.
Davies said: “We face an Ospreys side that is packed full of international talent and who have impressed this season to currently lie in fifth place in the table, just two points off a play-off berth.
“They also secured a big European scalp last week against Castres so will arrive full of confidence. We need to be ready to meet that challenge.
“We are looking to build and improve on the form that has seen us secure some important results over the last two months,” he added.
“We are under no illusions as to the size of the task that awaits us, but it’s an exciting way to finish 2013 at the Arms Park.”
Tickets remain on sale for the Welsh derby by calling 02920 302030 or clicking on www.cardiffblues.com/tickets
Cardiff Blues: 15 Leigh Halfpenny, 14 Alex Cuthbert, 13 Richard Smith, 12 Dafydd Hewitt, 11 Harry Robinson, 10 Gareth Davies, 9 Lloyd Williams; 1 Sam Hobbs (c), 2 Kristian Dacey, 3 Benoit Bourrust, 4 Macauley Cook, 5 Filo Paulo, 6 Andries Pretorius, 7 Rory Watts-Jones, 8 Robin Copeland.
Replacements: 16 Rhys Williams, 17 Thomas Davies, 18 Scott Andrews, 19 James Down, 20 Josh Navidi, 21 Lewis Jones, 22 Gavin Evans, 23 Chris Czekaj