Saints have been this season's surprise package and will kick off at St James' Park in third place in the Premier League table if Manchester United fail to win at QPR earlier in the day
However, the south coast club will be without a number of key players at St James' Park because of injury or international commitments.
Southampton's Victor Wanyama faces up to a month on the sidelines after suffering a hamstring injury in Wednesday's 1-0 FA Cup third-round replay victory at Championship side Ipswich Town.
Fellow midfielder Morgan Schneiderlin missed that game, and will be out for a similar spell because of an adductor problem.
Defender Toby Alderweireld is also missing through injury at a time when Sadio Mane and Emmanuel Mayuka are away on Africa Cup of Nations duty, and Maya Yoshida is with the Japan squad for the Asia Cup.
It all adds up to a challenging spell for manager Ronald Koeman, who saw his full-strength side beat Newcastle 4-0 at St Mary's Stadium in August.
Jack Cork was a scorer in that game and the midfielder, who has been sidelined through injury since early December, might have to make a comeback ahead of schedule.
Koeman was confident Cork would be ready if needed, saying: "It's not too early because Jack played last Monday 45 minutes in the Under-21 game against Fulham.
"He will miss having the rhythm of some games but he is in good shape
He's fresh, and we will need Jack in the coming games that we have," the Dutchman added.
- Window shopping -
Eljero Elia is also set to play at Newcastle having missed the Ipswich game because he had not signed on loan from Werder Bremen in time for the initial Cup tie.
The Dutchman made his debut at Manchester United last week and helped Saints to a memorable 1-0 win -- their first at Old Trafford since 1988.
Koeman said he might have to change his initial conclusion that the squad would not need new recruits during the January transfer window.
"I think now we can handle it but one or two injuries more we have to do something," he said
"But we will see."
After successive 4-0 away defeats at the hands of Southampton, Newcastle will hope to continue their impressive home form against the Saints.
Southampton haven't won in 11 games at St James' Park since March 1997, a sequence Newcastle will look to extend as they continue their search for a full-time successor to head coach Alan Pardew, who left to join Premier League rivals Crystal Palace earlier this month.
Caretaker boss John Carver has been forced to defend Newcastle's imminent training trip to the United Arab Emirates, amidst claims by supporters that it amounts to little more than a holiday for the squad.
Newcastle are without a game next weekend due to being out of the FA Cup, and will use their time to undertake a four-day training camp in Dubai, flying out on Sunday.
"People will be putting two and two together and thinking it's a holiday," said Carver
"But let me tell you, it's no jolly-up, and there will be curfews.
"I will treat the players with respect, but if anyone oversteps the mark or breaks the curfew then they will be fined
It's just like a normal week, and will mirror our regular work here at the training ground."
Source : AFP