Spurs are back among Europe football's elite after a 48-year absence and travel to Bremen's Weserstadion without England striker Jermain Defoe who has been ruled out for up to three months with ligament damage.
England defender Matthew Dawson is also missing with a medial ligament injury and both are expected to miss Tottenham's entire Champions League group stage programme.
Bremen are without centre-back Per Mertesacker who fractured an eye-socket playing for Germany in a Euro 2012 qualifier last week. Brazilian defender Naldo and striker Claudio Pizarro may miss the game as they struggle to overcome knee injuries.
Even with defenders Mertesacker, and possibly Naldo out, Bremen can rely on their second-string defence as Sebastian Prödl und Petri Pasanen kept Bayern Munich's star-studded attack at bay recently.
Tottenham manager Harry Redknapp has admitted he has concerns ahead of the game after playmaker Luka Modric limped out of the 1-1 draw at West Bromwich Albion on Saturday. But Redknapp also gave debuts to new signings midfielder Rafael van der Vaart and former Arsenal defender William Gallas who look set to play in Bremen.
In contrast, a patched-up Bremen side held defending Bundesliga champions Bayern Munich to a goalless draw at home on Saturday.
Bremen have new signings of their own in ex-Arsenal defender Mikael Silvestre and Brazilian play-maker Wesley.
This will be Spurs' first major European appearance since the 1961/62 season when they reached the semi-finals of the European Cup before losing to Benfica.
Bremen, by contrast, are back in the group stage after an absence of only 12 months, their failure to qualify last term halting a sequence of five consecutive appearances.
This is the first meeting between two teams who both qualified through the play-offs.
Bremen, third in the Bundesliga last term, defeated Sampdoria 5-4 on aggregate, winning 3-1 at home before losing the return 3-2 after extra time in Genoa.
Redknapp's Tottenham, who finished fourth in the Premier League in 2009/10, also suffered a 3-2 away defeat in their play-off against Swiss side Young Boys, but bounced back with a 4-0 home victory in the second leg.