Midfielder Guly do Prado underwent knee surgery on Wednesday and will be ruled out for the remainder of 2013.
Danny Graham is available for Hull after being ineligible to face parent club Sunderland last weekend.
The game may come too soon for Robbie Brady, while Sone Aluko's torn Achilles tendon means he joins James Chester and Allan McGregor on the sidelines.
MATCH PREVIEW
Southampton's morale will be sky high ahead of this game following the inclusion of Jay Rodriguez, Adam Lallana and Rickie Lambert in the England squad.
It's further reward for a team who've really impressed this season and lie sixth in the table after the second-best start to a top-flight campaign in the club's history.
Mauricio Pochettino's arrival in January was sceptically received by many at the time, but he's clearly taken the side to another level and it's the solid English core that excites Three Lions boss Roy Hodgson.
Rickie Lambert has already had a taste of international football, but what an opportunity for Rodriguez and Lallana to put themselves in the mix for Brazil next summer.
There's more to come from the south coast too, with Hodgson saying full-back Nathaniel Clyne is in his thoughts, while James Ward-Prowse and Luke Shaw are in the under-21 squad.
Southampton are becoming quite the England production line and we shouldn't forget some of those who've already come through the system with great success, such as Theo Walcott, Alex Oxlade-Chamberlain and Welshman Gareth Bale.
It's all a far cry from how things looked after just 13 seconds last Saturday, when Artur Boruc was beaten by Asmir Begovic's freak goal for Stoke.
Southampton recovered from that early shock to earn a point. They've only lost twice since the start of the season - at Norwich in the league and Wednesday's League Cup defeat at Sunderland, when a much changed line-up was fielded.
Hull travel to St Mary's with manager Steve Bruce unashamedly focusing on survival in their first year back in the Premier League.
Last week's 1-0 win over the nine men of Sunderland continued their solid home form, but they've lost four out of five on the road so far.
It'll be hard for them here against a team unbeaten in their last half dozen at home in the league.
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