Veteran full-back Murty joined Saints on a free transfer this week after being released by Reading at the end of last season and he is expected to go straight into the starting line-up.
Left-back Harding is also expected to start after completing a move to St Mary's from Championship side Ipswich over the summer.
Boss Alan Pardew had also hoped to included Radhi Jaidi in his side, but the former Birmingham defender's switch to the South Coast looks to be in doubt as he may struggle to obtain a work permit.
Young striker Kayne McLaggon is ruled out as he continues his recovery from a ruptured Achilles.
Pardew has been left short of options in attack following the departures of David McGoldrick, Bradley Wright-Phillips, Jason Euell and Stern John.
The match kicks off at 12.45pm.