Best, who played 35 minutes against Glasgow last Friday, will be joined in the front row by the returning Kyle McCall and Rodney Ah You, who has impressed at tight-head in the opening rounds.
Franco van der Merwe will captain the side in the absence of Rob Herring and Andrew Trimble, who will sit out this week due to squad management and recovery from a foot injury respectively. Franco will be joined in the second row by Alan O'Connor for the second week in succession.
The back row trio of Iain Henderson, Sean Reidy and Roger Wilson, which functioned so effectively in last week's victory in Glasgow, are retained.
Paul Marshall and Paddy Jackson will make up an experienced partnership at at half-back, with no less than 282 caps for the Province between them.
Charles Piutau has reverted to full back and will be joined in the back three by Louis Ludik on the left wing and Craig Gilroy, who missed out last week through injury, on the right.
Jared Payne will start the game at number 13 alongside Darren Cave, who shifts across to inside centre.
Tommy Bowe is in line to make his first appearance in an Ulster jersey in almost five months as he is named among the replacements alongside fellow backs Ruan Pienaar and Brett Herron.
John Andrew, Callum Black, Ross Kane, Kieran Treadwell and Robbie Diack will provide the forwards cover from the bench.
Ulster team and replacements to play Ospreys, Saturday 1st October, Kingspan Stadium (kick-off 6.30pm):
(15-9): C Piutau, C Gilroy, J Payne, D Cave, L Ludik, P Jackson, P Marshall;
(1-8): K McCall, R Best, R Ah You, A O'Connor, F van der Merwe, I Henderson, S Reidy, R Wilson;
Replacements (16-23): J Andrew, C Black, R Kane, K Treadwell, R Diack, R Pienaar, B Herron, T Bowe.