Like their opponents, Saturday's fixture also represents Southampton's first outing of pre-season, with the Saints looking to build confidence ahead of their Premier League campaign.
Match preview
After replacing Jesse Marsch as Leipzig boss in December, Domenico Tedesco is preparing for his first full season in charge of Die Roten Bullen.
Despite taking over halfway through the 2021-22 campaign, Tedesco certainly made an impact at the Red Bull Arena, guiding his side to their first-ever major trophy in May.
As well as lifting the DFB-Pokal, Leipzig also reached the Europa League semi-finals and finished the Bundesliga season in the Champions League places.
With Leipzig looking to clinch more silverware in the upcoming season, they have made a couple additions to the squad, with Janis Blaswich and Xaver Schlager arriving from Heracles Almelo and Wolfsburg respectively.
Die Roten Bullen also demonstrated their ambitions by locking down last season's topscorer Christopher Nkunku until 2026 after the Frenchman signed a contract extension last month.
While their opponents have made a couple of additions to their squad, Southampton have been particularly busy in the transfer market this summer.
Gavin Bazunu and Romeo Lavia have joined the club from Manchester City, while Armel Bella-Kotchap, Joe Aribo and Mateusz Lis have also arrived on the South Coast ahead of the new season.
After finishing in the bottom half of the Premier League table in the last five seasons, Southampton will be hoping that their new recruits can help the club clinch a top 10 spot.
With the Saints looking to enjoy a successful campaign, Ralph Hasenhutl will recognise the importance of integrating his new players into the squad over the course of pre-season.
The Southampton squad will certainly be busy in pre-season, with the Saints set to play RB Leipzig and Austria Klagenfurt in Austria before heading back to England to face Watford, Monaco and Villarreal.
Team News
With the Saturday contest representing their first friendly of pre-season, Tedesco is expected to give the majority of his squad playing time.
Josko Gvardiol and Konrad Laimer have been linked with moves away from the club, but the pair could feature against Southampton.
After scoring 35 goals in all competitions last season, Nkunku will be looking to get himself into goalscoring form in pre-season.
As for Southampton, they are expected to take a look at the majority of their squad on Saturday, which could result in Hasenhutl naming different teams for each half.
After joining signing for the Saints in the summer, Bazunu is expected to be given the number one shirt this season, with the Republic of Ireland international set to start in goal against Leipzig.
James Ward-Prowse is also expected to start on Saturday, and the Southampton captain could be partnered by Oriol Romeu in midfield.
RB Leipzig possible starting lineup:
Gulacsi; Gvardiol, Orban, Simakan; Klostermann, Kampl, Laimer, Angelino; Forsberg, Nkunku; Silva
Southampton possible starting lineup:
Bazunu; Walker-Peters, Stephens, Lyanco, Salisu; S. Armstrong, Ward-Prowse, Romeu, Djenepo; Redmond, A. Armstrong