The hosts overcame Dynamo Dresden 1-0 with 10 men in the cup, while Domenico Tedesco's side recently went down 5-3 to Bayern Munich in a pulsating Super Cup clash.
Match preview
Talk about staying up by the skin of your teeth - Pellegrino Matarazzo's Stuttgart side had their superior goal difference to thank as they ensured Bundesliga survival in the 2021-22 season, as they finished level on points with Hertha Berlin in the relegation playoff spot.
Retaining the services of Sasa Kalajdzic and turning Dinos Mavropanos's switch from Arsenal into a permanent deal has set Stuttgart up well for another year in the big time, but they certainly rode their luck against Dynamo Dresden in the first round of the DFB-Pokal.
After Darko Churlinov had given Matarazzo's side the lead, Stuttgart were forced to see out the final 25 minutes of the contest with 10 men after Waldemar Anton was sent for an early bath, but a 1-0 win was enough to kick off their 2022-23 campaign on a high note.
Pre-season was nothing short of perfect for Matarazzo, who witnessed his side claim four wins from four in July - including successes over Brentford and Valencia - although his side failed to keep a clean sheet in any of their friendly battles.
Defensive deficiencies were evident during the 2021-22 season too, as Stuttgart failed to keep a single clean sheet at home in the Bundesliga last term, and their chances of such a streak ending here are slim to none.
Entering the 2022-23 season with a shiny DFB-Pokal trophy to defend, RB Leipzig found themselves 3-0 then 4-1 down in the annual curtain-raiser against Bayern Munich before threatening the comeback of all comebacks against the perennial Bundesliga champions.
Despite Marcel Halstenberg, Christopher Nkunku and Dani Olmo's efforts, Domenico Tedesco's side failed to keep things tight at the back and paid for it, as Bayern struck five goals of their own to help Julian Nagelsmann get one over his old employers.
That 5-3 defeat represented the second game in a row that Leipzig had conceded a quintet of goals after going down 5-0 to Liverpool in their final pre-season friendly, and significant change has occurred at the Red Bull Arena since their fourth-placed Bundesliga finish last season.
The likes of Brian Brobbey, Nordi Mukiele and Tyler Adams have all moved on to pastures new, Konrad Laimer and Angelino could both still depart in the coming weeks, but Die Roten Bullen will at least enter the new campaign with Nkunku still on the books after his phenomenal 2021-22 exploits.
If ever there was a fixture to perk Leipzig fans up after a defeat, it would be this one, as Tedesco's side won both fixtures against Stuttgart last term by an aggregate scoreline of 6-0 and have only conceded one goal against their opening-day hosts since 2017.
Stuttgart form (all competitions):
RB Leipzig form (all competitions):
Team News
Stuttgart defender Anton will be fine to line up here despite his red card against Dresden, which will instead carry over to his side's next DFB-Pokal outing, and there is hope that star striker Kalajdzic will be fit for the contest after returning to team training from an ankle injury.
Much-coveted left-back Borna Sosa was another notable absentee from the DFB-Pokal showdown with an adductor issue and may only make the bench here given his lack of preparation, and the same can be said for Atakan Karazor.
Thomas Kastanaras, Tanguy Coulibaly and Nikolas Nartey are all expected to miss out for the hosts, who have now lost Orel Mangala to Premier League newcomers Nottingham Forest.
Meanwhile, Leipzig striker Alexander Sorloth is also back with the team in training after battling back from a foot injury, but Yussuf Poulsen (thigh) is unlikely to be involved just yet.
Josko Gvardiol also missed the Super Cup defeat to Bayern with a muscular problem and will likely remain sidelined for this one, as Leipzig seek to fend off interest from the Premier League for his services.
Angelino is unlikely to be involved amid rumours of a switch to Hoffenheim, while Ademola Lookman has now signed for Atalanta BC in Italy, but Laimer was a starter in the Super Cup despite speculation surrounding his future.
Stuttgart possible starting lineup:
Muller; Mavropanos, Ito, Anton; Vagnoman, Ahamada, Fuhrich, Endo, Silas; Tomas, Kalajdzic
RB Leipzig possible starting lineup:
Gulacsi; Klostermann, Orban, Simakan; Henrichs, Laimer, Haidara, Raum; Olmo, Szoboszlai; Nkunku
We say: Stuttgart 1-3 RB Leipzig
While a Kalajdzic-inspired Stuttgart can feel optimistic about their chances of breaking down a Leipzig defence that has shipped goal after goal already this summer, the towering Austrian may not be in peak physical condition for the opening day.