Last season, the two sides shared six goals in Hampshire but the Town won the home game by three goals to one. The Saints finished in fourth spot last season, three points behind third-placed Town.
With manager Steve Robertson on holiday, the team will have former Town player and captain Kim Reeves looking after affairs. Kim said: "After some tough pre-season fixtures, the girls are keen to get the season started. They have worked hard and feel that they can build on last season when they narrowly missed out on promotion.
"Southampton are a strong, well-organised side who will be looking to push for honours. I think that this year it will be a tough league with several sides challenging for top spot, so every point will be vital."
The Town have included new signings Abby Picton from Cardiff Met and Northern Ireland international Alex Hurst from Bristol Academy in Sunday’s squad.
SQUAD: Robyn Levett, Alice Smith, Alex Hurst, Sam Quinn, Ellie Maynard, Meg Vella, Laura Morgan, Sarah Uzzell, Chyna Collings, Michelle Rich, Beth Westlake, Serena Smith, Megan Attenborough, Abby Picton, Chenise Austin & Sally Butterfield.
Sunday’s game will be played at Shrivenham FC, Barrington Park, Shrivenham SN6 8BJ and will kick-off at 2pm.