Freiburg finished the 2019-20 campaign in eighth place - only one point below Wolfsburg in the final Europa League qualification spot.
Stuttgart are back where they belong. The five-time Bundesliga champions ensured that their stay in the second division was a brief one as they secured promotion straight back to the big time last season.
Pellegrino Matarazzo's side ended up 10 points adrift of champions Arminia Bielefeld, but Stuttgart nevertheless managed to finish as runners-up by a margin of three points above Heidenheim, who ultimately lost to Werder Bremen in the promotion/relegation playoff.
Stuttgart were champions of Germany as recently as 2007, but a rapid decline in the early 2010's saw Die Schwaben drop down to the second tier in 2016 before another relegation from the Bundesliga occurred in 2019.
Matarazzo will be keen to avoid another underwhelming top-flight campaign for Stuttgart, but the newly-promoted outfit enjoyed a solid pre-season with victories over Arminia, Hamburger SV and Strasbourg after a 3-0 loss to Liverpool at Anfield.
Stuttgart's first-round match in the DFB-Pokal saw them travel to third-tier Hansa Rostock, and a Silas Wamangituka goal was enough to send Die Schwaben through to the next stage last weekend.
Meanwhile, Freiburg only lost one of their last five games in the disrupted 2019-20 season, but Christian Streich's side ultimately missed out on a Europa League place by a solitary point.
The disappointment of losing out on a spot in international competition by such a narrow margin would have been extremely hard to take, but Freiburg will no doubt be motivated to go one better this time around.
However, Breisgau-Brasilianer's away form is a cause for concern heading into the opening weekend - Streich's men triumphed in their first three away games of the previous campaign before winning just one of their next 14.
Like Stuttgart, Freiburg also enjoyed a one-goal victory against a third-tier side in round one of the DFB-Pokal, with Jonathan Schmid's 79th-minute winner paving the way for a 2-1 win for the Bundesliga outfit against SV Waldhof Mannheim last Sunday.
The two sides played out 3-3 and 2-2 draws in the 2018-19 Bundesliga campaign, but Freiburg have not beaten Stuttgart in the top flight since 2012 - a run of nine games without a win against Die Schwaben.
Stuttgart form (all competitions): W
Freiburg form (all competitions): W
Centre-back Konstantinos Mavropanos has arrived on a season-long loan from Arsenal, but the 22-year-old is fighting to overcome a groin injury.
Given the long list of injured players, Matarazzo is unlikely to make many changes from the side that beat Hansa Rostock at the weekend.
As for Freiburg, goalkeeper Mark Flekken is out after injuring his elbow, while the game is expected to come too soon for defender Janik Haberer, who is nursing an ankle injury but is also being tipped to leave.
Fellow defender Keven Schlotterbeck missed out the cup victory and may not be involved in this one either.
Freiburg recently welcomed Baptiste Santamaria to the club from Angers, and the midfielder could make the squad for the trip to Stuttgart.
Stuttgart possible starting lineup:
Kobel; Anton, Kempf, Kaminski; Stenzel, Mangala, Castro, Sosa; Wamangituka, Didavi; Kalajdzic
Freiburg possible starting lineup:
Muller; Schmid, Lienhart, Heintz, Gunter; Sallai, Hofler, Santamaria, Grifo; Petersen, Holer
We say: Stuttgart 1-2 Freiburg
Stuttgart's remarkable home record coupled with Freiburg's woeful away form, on paper, makes for an easy win for the newly-promoted side. However, Stuttgart are going into the opening weekend with a heavily-depleted squad while Freiburg will look to get off to a fast start in their quest for European football, so we are backing Streich's men to take all three points in a closely-fought encounter.