A Timo Werner penalty has handed Leipzig an advantage ahead of the second leg, meaning that Spurs have work to do if they are to progress to the quarter-final stage of the competition.
It would be fair to say that Leipzig are not considered to be among the favourites to win the Champions League this season, but the Bundesliga giants are certainly a side to be taken seriously in the competition.
Third in the Bundesliga with 50 points from their 25 matches, Leipzig are unbeaten in their last six matches in all competitions but were held by Wolfsburg in the league on Saturday.
The first leg of this contest actually proved to be the first time that the German side had faced Tottenham in any competition and indeed the first time that they had locked horns with English opposition.
Julian Nagelsmann's side finished three points clear at the top of Group G to progress to this stage, and they have now won six of their 13 Champions League matches. That said, the German team have won just one of their last four home European games, which is a record that will hand Spurs confidence.
Werner scored the only goal of the match at the Tottenham Hotspur Stadium, and the 24-year-old, who continues to be linked with Liverpool, will be looking to add to his 27 strikes for the season in this game.
Tottenham, meanwhile, will enter this match off the back of a five-game winless run, suffering four defeats across three separate competitions in the process.
Spurs twice lost to Bayern Munich in the group stages of this season's Champions League but still comfortably qualified for the knockout stage. They reached the 2019 European Cup final after beating Borussia Dortmund, Manchester City and Ajax in the latter stages before losing out to Liverpool.
It is difficult to imagine the London club making a strong play for this season's crown even if they manage to progress from this tie, though. Spurs have lost seven of their 14 European matches on German soil although five victories have arrived during the same set of fixtures.
Leipzig Champions League form: LWWDDW
Leipzig form (all competitions): DWWWDD
Tottenham Champions League form: LWWWLL
Tottenham form (all competitions): WLLLLD
Kane and Son, as mentioned, remain on the sidelines for Tottenham, while powerful midfielder Moussa Sissoko is still on the treatment table following a knee operation.
Juan Foyth could potentially return as he battles back from a groin problem, but January arrival Steven Bergwijn will miss out with the ankle injury that he picked up against Burnley. Indeed, the Dutchman faces a battle to play again this season due to the seriousness of the issue.
Leipzig possible starting lineup:
Gulacsi; Klostermann, Upamecano, Halstenberg; Mukiele, Laimer, Sabitzer, Angelino; Werner, Schick, Nkunku
Tottenham possible starting lineup:
Lloris; Aurier, Sanchez, Alderweireld, Vertonghen; Lamela, Winks, Lo Celso, Sessegnon; Alli, Lucas
We say: Leipzig 2-1 Tottenham
Tottenham are certainly capable of turning things around in Germany, but it is difficult to imagine Mourinho's side picking up the result that they need due to their absences in the final third of the field. We fancy Leipzig to win on the night and therefore book their spot in the quarter-final stage of the competition.