This season looks certain to be Anelka's last at Stamford Bridge, while there is increasing uncertainty over the future of Drogba, who has yet to agree a new deal.
Villas-Boas revealed this week that Kalou had also been offered a contract extension, but time is running out for Chelsea to secure these assets, each of whom will be able to negotiate a free transfer at the turn of the year.
But despite the club reporting losses of £70.9million in their last annual accounts amid the new era of Financial Fair Play, Villas-Boas insists they would not need to sell.
"I don't think so, it happens all the time," said the Blues boss, pointing out he encountered a similar scenario at Porto last season.
"The most important thing is for the club to try to defend its interests. We know these players are of higher importance.
"That's why the offers are on the table, apart from with Anelka, end of story.
"We will try to get them to reach an agreement."
Should all three move on, Chelsea would go from having an embarrassment of riches up front to arguably lacking numbers.
"That's why the talks are ongoing," Villas-Boas added. "We still have plenty of time."
Indeed, two and a half months must seem like an age to Villas-Boas celebrated his second anniversary as a manager on Friday.
The Portuguese, who also turns 34 on Monday, has packed a remarkable amount into his short career, transforming the fortunes of Academica before leading Porto to an incredible quadruple.
And he has revealed he might even have taken a different path had he accepted an offer to join Sporting Lisbon shortly after becoming a manager.
"I was two weeks into a job and I was being offered a job at Sporting Lisbon," he said before explaining why he stayed put.
"First, there wasn't an agreement for compensation for Academica. Eventually, the decision came to me and I didn't want to go. I felt well where I was."