Mauricio Pochettino will be hopeful his team's exertions against the most successful side in European club competition won't have too much of an impact on his players and they're able to go into the international break with all three points in the bag.
After all, they followed up their 1-1 draw in the Santiago Bernabéu with a 4-1 win over Liverpool at Wembley before West Ham United came from behind to knock them out of the Carabao Cup.
Spurs can't afford to be inconsistent, especially when there's a chance they can gain points on their rivals this weekend with Manchester City playing host to Arsenal and José Mourinho returning to Stamford Bridge.
Pochettino will no doubt fancy his chances against Roy Hodgson's team. The Eagles have won just one game all season – albeit that was a 2-1 win over champions Chelsea – and did come from 2-0 down to draw with West Ham United last weekend. However, they're yet to keep a clean sheet this campaign and have scored just three Premier League goals.
Spurs are without a clean sheet in five matches but may feel like a shutout is on the cards against Palace, even without the injured Toby Alderweireld after the Belgian injured his hamstring in the win over Real Madrid.
Eric Dier is likely to replace him on the right side of the Spurs back three with Serge Aurier coming in at right wing-back to replace the impressive Kieran Tripper as Pochettino continues to rotate his full-backs.
Harry Kane will want to get back to scoring ways after retuning to the starting XI against the La Liga champions but failing to put the ball in the back of the net.
Our unique algorithm has predicted the Spurs side it believes is most likely to start.
Football Whispers uses data to predict the starting line-ups for sides by accounting for a number of different factors, including injuries, suspensions, the statistical likelihood to play, the match the competition is played, the player’s previous performance and the style of the opposition.
But you can also give it a go yourself. Just click ‘create your own’ on the line-up at the top of the page and pick the XI players you would choose, and you can also see their stats once you’ve picked them.