Ospreys have won all four home games at Liberty Stadium this season in all tournaments, tallying 31 tries and conceding just five.
Ospreys only defeat in their last nine encounters with fellow Welsh regions was 16-25 at home to Scarlets in March.
Newport Gwent Dragons' only victory in their last six matches was 37-16 at home to Brive in the European Challenge Cup.
Dragons have lost their last four Guinness PRO12 encounters since beating Zebre at Rodney Parade in round 2.
They have not won away from home in the Championship since a trip to Treviso in March 2015.
Dragons most recent success over a fellow Welsh region in the PRO12 came on a trip to Cardiff on Boxing Day 2014.
Ospreys have won their last nine fixtures against Dragons since their neighbours to the east won by a single point at Rodney Parade on 6 January 2012. Dragons' only previous victory at Liberty Stadium was 21-16 in October 2010.
Overall Guinness PRO12 head to head record:
Played 26, Ospreys won 17, Dragons won 9.
At Liberty Stadium, 3pm Live on S4C and Sky Sports
Referee: Ben Whitehouse (WRU, 31st competition game)
Assistant Referees: Ian Davies, Wayne Davies (both WRU)
Citing Commissioner: Gwyn Bowden (WRU)
TMO: Gareth Simmonds (WRU)
Guinness PRO12
Suite 208, Alexandra House,
The Sweepstakes
Ballsbridge, Dublin 4, Ireland