Harry Kane has been ruled out of Tottenham's match at Manchester United on Saturday with a minor hamstring strain sustained against Liverpool last weekend.
Kane was replaced for the final two minutes of the 4-1 win at Wembley, clutching his left hamstring, but afterwards Spurs manager Mauricio Pochettino insisted he was "just tired."
But Kane missed Wednesday's 3-2 defeat to West Ham in the Carabao Cup and he is now out of the match at Old Trafford.
Pochettino told his prematch news conference on Friday: "For tomorrow, we cannot take a risk. It's a minor injury, very small, but we cannot take a risk. We'll see after for Wednesday against Real Madrid. Tomorrow, it's impossible."
Spurs are level on points with second-placed United but they will be considerably weaker without Premier League top scorer Kane, who already has eight goals in nine league appearances and 13 in 12 for Spurs so far this term.
Asked if the injury was a major blow for his team, Pochettino added: "Yes, you always want all the players available. It's a problem. We want them available to play.
"We always believe in the collective, the squad. During the season, problems happen and you must trust all the players, all the squad. I told the players are not machines and its so difficult to cope with international duty, play every three days. It's lucky it's not a big problem but he's not going to play tomorrow."
Pochettino said he would not make a decision on what formation to field in Kane's absence against Jose Mourinho's side until the morning of the match.
"Today is the second day after West Ham game so it's difficult," he said. "We need to wait until tomorrow to decide the formation. We can use different formations, we worked a lot on it in preseason. The players can adapt to one or another shape. We need to assess everyone and make a decision to be competitive.
"United have one day more rest, an advantage, to prepare. We're on the limit and it's so important because after we play Real Madrid on Wednesday and finish aga