The striker had to be replaced in the first half of Tottenham's 1-0 win over West Brom with an ankle injury which is likely to keep him out of action for around three weeks
A second-half strike from Gareth Bale gave Spurs three vital points at the Hawthorns, although they had to do it without the striker, who had to be replaced by Lewis Holtby after 39 minutes.
Speaking after the match, Defoe's manager Andre Villas-Boas said he expected to be without his forward for around three weeks, although only a scan would reveal the true extent of any damage.
“He is definitely out of the England squad and our Newcastle game for sure,” Villas-Boas said to Sky Sports.
“We just have to scan it, but at the moment it doesn’t look too good. Normally it is the ligament on his ankle and this should keep him out for around three weeks.
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“Hopefully there is not any extra damage but only when we have the scan will we be able to know for sure.
“Now we just have to focus on getting him back and continue to work with the options we have.
“Clint Dempsey is a different type of striker if we play him there and it will require a certain level of adaptation but I think we can make it work.”
The Portuguese boss said he was happy with the way Tottenham played in the narrow win and said it represented a good week following the midweek draw against Norwich City.
Villas-Boas said: “We were the better team and we managed to create a lot of chances.
“We went through a difficult time without a striker where we had to move Clint Dempsey into the striking position but I think it was a job really well done by the boys.
“It is very difficult when you play two Premier League games in a short space of time and it’s very important to get four points from two tough away games, that’s good for the team at this stage of the season.”