The Tottenham striker is expected to miss both Europa League quarterfinal legs against Basel, as well as the league clash with Everton on Sunday, due to a muscle problem
The muscular problem means the diminutive forward will miss his side’s Europa League quarterfinal with Basel and the critical league clash with sixth-placed Everton on Sunday.
Defoe could be fit for Manchester City's visit to White Hart Lane in three weeks, but until then the north London club must rely on its only remaining recognized striker, Emmanuel Adebayor.
"Jermain has a muscle injury which is probably going to take him out of the next two games definitely and maybe Basel away," Villas-Boas told reporters ahead of the first-leg clash against Basel.
"If he can't make Basel away he should be fit for Man City.
"It's a big blow. It's on the same muscle that he had a small tear last month. It's on the other side now and it's a big miss as he represents a lot for us and he will be a big miss."
The 30-year-old has struggled with injuries throughout the season and has failed to find the net since Boxing Day – though he has started just seven league games in that time.