The Manchester United striker suffered a thigh strain when he was taking the corner for Phil Jones' winner against Shakhtar Donetsk at Old Trafford on Tuesday.
It was only Van Persie's second game back after a fortnight's absence with groin and toe complaints and came after he had been on the pitch for barely four minutes.
Now United will be without him for the entire Christmas period, plus vital matches in the FA and Capital One Cups.
And Moyes can only hope his side do not miss him as much as they have done in recent weeks.
"It is a blow to lose Robin because he is so influential," said Moyes.
"Think of the games that have been tight, even in the last week or so. Last year he was the one who was nicking the winner in a lot of those games.
"It could have made the difference when we were trying to get a goal against Everton."
There have been suggestions Van Persie is not too impressed with Moyes' training regime.
If that is true, the manager is unaware of the complaints.
"Robin has been great to work with," said Moyes.
"We have looked after him and tried to train him and do it the way he needs to work.
"I am sure he would be the first to accept it."
With Van Persie missing, Wayne Rooney must continue to drag United forward, as he has done for most of the season.
The England forward's contract runs out in 2015 and with renewed suggestions about a bid from Chelsea, United could be forgiven for getting somewhat nervous about Rooney's future.
Instead, Moyes is relaxed.
"The club are comfortable," he said.
"Lots of discussions have gone on between the club and his representatives.
"I think that is all fine. I don't see any great panic."
Rooney will start at Aston Villa on Sunday, when United will attempt to get their Premier League campaign back on track after successive home defeats sent them spinning down into ninth spot.
"There is a real toughness about the players to put it right," said Moyes.
"I see that in them. They know the standards they have set over the years and when we haven't won they have been distraught."