The two sides had contrasting fortunes last season, with Southampton finishing in seventh to secure a Europa League spot, while Newcastle needed a win on the final day of the season to secure their top-flight status for another year.
It has been a summer of change for Newcastle United, with John Carver being dismissed after narrowly keeping the side in the Premier League, resulting in Derby County manager Steve McClaren taking over as manager.
A number of players have also left the club in the summer, with Jonas Gutierrez, who scored in their survival-confirming win over West Ham United last May, among those released at the end of their contracts.
McClaren has been given plenty of funds to bring new players in though, spending a total of almost £40m to secure the services of midfielder Georginio Wijnaldum, striker Aleksandar Mitrovic and defender Chancel Mbemba, while forward Ivan Toney also comes in for an undisclosed fee from Northampton Town.
The club's fans have become increasingly disenchanted with owner Mike Ashley in recent years, with fans protesting against the businessman's reign at the team last season. He will be hoping that investment and results on the pitch will get the supporters back on side.
With Hull City losing on the final day of the season, the Magpies did enough to finish four points clear of the relegation zone, securing a 15th-place finish. Defending was the main issue for Newcastle last season, with the team conceding 63 goals and keeping just eight clean sheets; only relegated Queens Park Rangers had a worse record.
The hosts will be hoping for more goals too, netting just 40 in their 38 league games last season, with only five of their rivals scoring fewer, including two of the clubs that went down.
McClaren's men have not had the best preparation for the new season though, winning just once in their pre-season schedule, suffering a defeat to League Two side York City, and being held to a draw by League One's Sheffield United.
Recent form: LLLDLW
Recent form (all competitions): LWLDLL
Ronald Koeman announced his arrival in the Premier League in style, securing European football for Southampton in his first season managing in the English top flight.
The manager appears to have been pushing himself as hard as his players in preparation for the new season, as he ruptured his Achilles in training earlier this week, which could keep him out of the dugout for the trip to Newcastle.
Southampton had a tricky start to their pre-season fixture list, losing three straight matches, but a run of four wins, including a 10-0 thrashing of Dutch side Quick 20, plus a 1-1 draw with Espanyol should leave the visitors full of confidence.
Koeman has been busy in the transfer market too, strengthening his side with players like Jordy Clasie from Feyenoord and Malaga striker Juanmi, while defender Steven Caulker comes in on a season-loan loan. There have been a couple of high-profile departures for the South Coast side to deal with though, as Nathaniel Clyne has moved to Liverpool, while Morgan Schneiderlin left for Manchester United.
Southampton had one of the best defences in the league last season, with only champions Chelsea conceding fewer goals and keeping more clean sheets, while their 54-goal haul was the sixth best in the division.
Recent form: LWLLWL
Recent form (all competitions): WWWWDW
As well as the Achilles injury to their manager, Southampton have a number of players struggling with injuries coming into this match, but Clasie should be available again after sitting out a Europa League qualifier against Vitesse with a minor hamstring problem.
Gaston Ramirez and Ryan Bertrand have both been carrying knocks too, with the latter expected to miss the first few weeks of the season while recovering from minor knee surgery, but Jay Rodriguez will be available after recovering from a knee ligament injury and proving his fitness in pre-season.
Emmanuel Riviere will miss out as he may need surgery after injuring his knee on the club's tour of the US, while Paul Dummett will need a late fitness test to prove that his hamstring is up to the task.
Meanwhile, McClaren admits that he will have decisions to make over the inclusion of Aleksandar Mitrovic and Chancel Mbemba, who have had limited minutes since joining the club in the last few weeks.
Newcastle possible starting lineup:
Krul; Dummett, Haidara, Janmaat, Taylor; De Jong, Gouffran, Sissoko, Colback; Mitrovic, Cisse
Southampton possible starting lineup:
Davis; Yoshida, Fonte, Soares, Martina; Clasie, Mane, Ward-Prowse, Wanyama; Pelle, Juanmi
Head To Head
Southampton have had the better record against Newcastle over the last couple of years, winning their last three meetings against the Magpies, including 4-0 victories at home in the last two years, Newcastle's last win over Southampton was in 2013, when they secured a 4-2 victory at St James' Park
In last season's meeting at St James' Park, Eljero Elia netted a brace to set up a 2-1 victory for Koeman's side, while Yoan Gouffran scored for the hosts.
There has been little to separate the two teams over the years, with the Magpies winning 22 of their 57 previous matches, while the Saints have claimed 21, and 14 have resulted in draws.
We say: Newcastle United 1-2 Southampton
Southampton have had the measure of Newcastle for the last couple of years, and come into this match following a much stronger pre-season showing. Newcastle will be keen to impress under new manager Steve McClaren, but the visitors' solid defence should be able to do enough to stop their opponents.