Club captain Vidic is moving to Inter when his contract expires next month, while former England skipper Ferdinand has been released.
The duo formed a fearsome central-defensive partnership at Old Trafford following Vidic's arrival in January 2006, and United legend Neville believes losing both players at the same time could have a damaging effect.
"I think it's a big risk losing Vidic and Rio at the same time," Neville is quoted as saying in 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."
Neville went on to say he hopes new United manager Louis van Gaal spends wisely during the close-season after his predecessor David Moyes struggled in the transfer market.
"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."
