The England coach believes the departure of the pair will hit the club hard, despite new boss Louis van Gaal reportedly targeting centre-backs in this summer's transfer window
Vidic has agreed to join Inter, while Ferdinand announced recently that he would not be renewing his contract at Old Trafford.
The pair have won 11 Premier League titles between them and each played a key role in United's 2008 Champions League success, and Neville feels their respective departures will hit the club hard – despite the emergence of young trio Phil Jones, Jonny Evans and Chris Smalling.
“I think it’s a big risk losing Vidic and Rio at the same time,” the former right-back is quoted as saying by the Manchester Evening News.
“There are young centre backs coming through, Phil Jones, Jonny Evans and Chris Smalling. And I think if we’re signing a new centre-back coming from a different country who hasn't played here before, the idea of having a stalwart there would help.
“I think it’s a risk. But we’ll see how that pans out.”
New boss Louis van Gaal has been linked with a number of centre-backs, with Mats Hummels of Borussia Dortmund and Benfica's Ezequiel Garay both reportedly on his wishlist ahead of the summer transfer window but Neville does not believe the squad is in need of wholesale surgery.
“The club has spent quite a bit of money on Juan Mata and Marouane Fellaini, and I’m not sure whether, at this moment in time, those signings have taken us any further forward," he added.
“We've got some good players. We shouldn't be sweeping 10 players out of that squad. It should be done in a more organic fashion.”
And, despite the appointment of Van Gaal, Neville believes the Dutchman will have to wait to win his first Premier League trophy.
“At this moment in time we’re in a period of instability, I’m not saying we’re going to be champions next season, I think that would be too big of an ask," he said.