The two teams sit level on seven points at the top of Group H after three games ahead of Los Blancos' first ever visit to Wembley.
"It's not easy for everyone and, maybe, he was affected a little bit by that".
The Welshman has been out of action for nearly six weeks after sustaining a calf injury and missed Wales' final World Cup qualification clash against the Republic of Ireland. But taken together, they perhaps provide just the slightest cause for concern.
Davinson Sanchez is expected to return to the lineup and slot in alongside Toby Alderweireld and Jan Vertonghen in the back-three, while Danny Rose and Serge Aurier will likely start as wing-backs.
But Pochettino doesn't seem too worried. My feeling is good. As if that is not enough, both sides are eight points a drift of their respective league leaders in FC Barcelona and Manchester City!
However, this is a really tough game. 'Maybe it's possible for him to play but I don't want to say 100 per cent'. Liverpool grabbed a much-needed 3-0 win over Huddersfield Town in the Premier League on Saturday to bounce back from a 4-1 defeat by Tottenham.
The bottomless pits of money that Tottenham's rivals own can offer outrageous wages to their players - and with interest high in Pochettino's stars, many expect an exodus of playing staff to leave the club soon. Whilst in the last campaign, Victor Wanyama came in and was hugely impressive.
Here, Sportsmail tells you all you need to know about the European showdown.
Madrid are [2.2] to win outright, which may tempt some, but a more profitable way to approach the away victory is via the Correct Score market.
So far in this group, both sides have identical numbers.
The France international was considered a doubt and trained alone on Monday.
Wednesday's return at Wembley looks to be another tense affair, particularly with the two clubs coming off the back of defeats at the weekend. Each has five goals to his name and can be backed at [1.88] and [1.7] respectively to notch.
The reigning La Liga champions continue to be heavily linked with the prolific Tottenham striker, who has been billed as a natural successor to Cristiano Ronaldo in the Spanish capital.