Richarlison suffered a calf injury against former club Everton in the Premier League on Saturday and was substituted after 52 minutes.
Tottenham went on to win 2-0, with Harry Kane converting a penalty and Pierre-Emile Hojbjerg adding a second.
The Brazilian has scored two goals and provided two assists in 13 appearances for Tottenham since joining for £60m from Everton in the summer.
"For sure he's out. He felt something in his calf and he won't be available," said Spurs manager Antonio Conte.
"I think he needs a bit of time to recover. It's a pity because we are talking about a player who gives us a lot of quality but is also strong and improves our intensity.
"He will have an MRI to understand it tomorrow, we hope it is not serious."
With just over a month away before the FIFA World Cup gets underway in Qatar, Richarlison looked downhearted after being forced off as he awaits the results of a scan.
"It's kind of hard to say because it's so close to realising my dream [playing at the World Cup]," he told ESPN Brasil. "I've already suffered an injury similar to this, I hope it can heal as soon as possible, or less. I was stopped about two months at Everton.
"I know it's hard to talk right now, but let's see, I'll recover. Monday I have tests to do, but even walking hurts. Let's wait.
"It's all so close, it's about a month to go, and we've been getting ready, working every day so that nothing serious can happen. Unfortunately, today I had this calf injury, but now it's just a matter of waiting, doing the treatment every day so that I can recover as soon as possible.”
