Ferguson wants to keep the 40-year-old, who is retiring at the end of this season, fresh for the May 28 Champions League Final against Barcelona and hopes his team can pick up the point they need for the domestic title without him.
"I'm going to rest Edwin van der Sar tomorrow given the programme he's been through in the last few weeks," Ferguson, seeking a 12th Premier League title with the club, told a news conference on Friday.
"He's played every game... we have an opportunity to give him a break."
A draw against struggling Blackburn would seal a record 19th English league title, while if they should lose they could still secure it on Sunday if Chelsea do not beat Newcastle United. There is still a final round of games next Sunday.
On paper it should be a simple job, with United having hammered Blackburn 7-1 earlier in the season thanks to five goals from Dimitar Berbatov but with the hosts involved in the relegation battle Ferguson is not expecting an easy ride.
"We're going to play our strongest team. It's a big game. It's always a difficult game at Blackburn," he said. "They are also fighting, I think they probably need a point."
Midfielder Darren Fletcher should feature against Blackburn as he continues his comeback from a virus that sidelined him for two months and Ferguson hopes he can be fit in time to face Barca, having missed the 2009 final through suspension.
"We've got to give him a chance (to get back in time). He is back training every day, he's over his virus he had," said Ferguson, adding that Fletcher had come through more than an hour in a reserve game against Blackburn this week.
"It's a matter of getting the strength and speed to his game and we have some games to try and do that. I think he'll go very close, the boy's got application and the desire to do it and hopefully we can get him there."
United top the table with 76 points from 36 games, with second-placed Chelsea on 70 and third-placed Arsenal on 67.
Winning the title would see United break the record of 18 they share with bitter rivals Liverpool. Clinching it on Saturday could also steal some thunder from neighbours Manchester City, who play Stoke City in the FA Cup Final the same day.
