Jose Mourinho's men enter the game at Turf Moor on the back of four successive defeats in all competitions.
Before that trip to the Red Bull Arena, the Lilywhites must first attempt to get their top-flight campaign back on track when heading to Burnley.
Here, Sports Mole looks at how Mourinho may set out his side.
Mourinho has admitted to being "really worried" about his side's quick turnaround in fixtures, with the trip to Leipzig coming three days after this showdown at Burnley.
Rotation can be expected between the two matches, though a lack of other options could see the Portuguese revert back to the same front three used in the 3-2 loss to Wolverhampton Wanderers.
That would mean academy product Troy Parrott, given a chance in the cup exit to Norwich, dropping back out of the side.
Hugo Lloris has missed Spurs' last two games with a groin problem and is not expected to return this weekend, while Ryan Sessegnon and Erik Lamela are also fitness doubts.