Many Saints fans will be making the same trip as three of their team's former favourites, swapping Southampton for Merseyside (albeit for a day).
Former Southampton stars Rickie Lambert, Adam Lallana and Dejan Lovren have all made the switch from the south coast to join up with Liverpool. However, only two of them are in line to face Ronald Koeman's men after Lallana suffered a knee injury during pre-season.
There's a sense of karma among Saints fans, with Lallana's injury being added to a long list of bad fortune suffered from the Hampshire club's summer defectors.
Lovren could only train with Liverpool's youth team this summer after his US Visa was refused, prohibiting him from joining up with his teammates on their tour of the USA. Lambert, after scoring all 34 of his Southampton penalties, also managed to miss from the spot on that American tour. Meanwhile, Luke Shaw - who joined Liverpool rivals Manchester United - was accused by boss Louis Van Gaal of lacking fitness, before breaking down with an injury that has ruled him out for four weeks.
The Southampton team to face Liverpool has had to go through a massive overhaul to cope with the loss of so many key players in the summer. Saints have made several summer signings, including Fraser Forster, Ryan Bertrand, Dušan Tadić, Graziano Pellè, Saphir Taïder, Shane Long and Florin Gardos. All seven players will be vying for first team spots for Sunday.
There are also plenty of young players from Southampton's esteemed football academy who will be looking to make the step up into first team football. We could well be seeing regular first team action for James Ward-Prowse, who has impressed whenever he's been given the chance, while the likes of Lloyd Isgrove and Matt Targett have really impressed during Saints' pre-season schedule.
Southampton looked good during their European and domestic tours during the summer, compiling five wins from six games - the one loss coming from German giants Bayer Leverkusen. Koeman will be hoping to take that form into a season with a distinct sense of uncertainty.
Obviously, there are questions as to how this quickly-assembled side will perform in such a competitive league, while there are still doubts surrounding the future of two more of Saints' stars; Jay Rodriguez and Morgan Schneiderlin. Ex-Southampton boss Mauricio Pochettino's Tottenham Hotspur have been linked to signing both Jay Rod and Schneiderlin: while there is nothing to suggest the former wants to leave as he battles to regain fitness following a knee injury, the latter has been very vocal about his desire to leave Hampshire for London.
Koeman hasn't been able to use Schneiderlin in any of his pre-season games due to his World Cup commitments with the France National Team, before the Dutch coach was unable to field the 24-year-old midfielder against Leverkusen as he wasn't "physically or mentally fit enough" to face the Germans. There are still doubts this has changed and it would certainly be a surprise to see him lace up his boots to face his former teammates at Anfield on Sunday.
New Saints boss Koeman has been using a blend of 4-3-3/4-5-1 formations during pre-season, with less focus on pressing compared to his predecessor Pochettino. Liverpool have also looked good in their summer tour of the States, playing in a similar vein to that of last season.
Liverpool took the spoils at St Mary's last season, while Southampton were one of two sides to defeat Liverpool in their own back yard in 2013/2014. This, along with the added spice of Liverpool's policy of signing anything from Southampton this summer, makes for a fascinating first game of the Premier League season for both teams.