Southampton will be without Lee Barnard and Morgan Schneiderlin when they host Tranmere.
Striker Barnard is sidelined with a hand injury suffered in an off-field incident and midfielder Schneiderlin is on international duty with the France Under-21 squad.
David Connolly is not expected to return from a stomach injury in time so Rickie Lambert is the only available senior striker.
Lambert may therefore play up front on his own, or midfielders Adam Lallana or Jason Puncheon could be pushed further forward to join him.
Schneiderlin's absence means a first start for Richard Chaplow, who recently arrived at St Mary's on loan from Preston.
Midfielder Paul Wotton (back) and full-back Frazer Richardson (shoulder) are still on the sidelines.
Tranmere striker Ian Thomas-Moore could return to action when his injury-hit side make the trip to Southampton.
Thomas-Moore has missed the last two games with a thigh injury sustained late in the game at Colchester but he returned to training on Thursday.
Veteran defender Ian Goodison is unavailable while he serves a one-match ban for collecting five yellow cards, so Nick Wood will come into the side for his fifth start of the season.
However, boss Les Parry could again be without the likes of Gunnar Nielsen, Marlon Broomes, Ash Taylor, Liam Darville and Alan Mahon, who are all nursing injuries.
Parry - whose side currently lie in the relegation zone - said: "The only player who has a chance of coming back into the squad is Ian."