Successive home defeats against Everton and Newcastle United have ramped up the pressure on manager David Moyes, with last season's English champions now without a win in four league games.
United have slipped to ninth in the table as a result – 13 points behind leaders Arsenal – and will be without a host of key players for their road trip.
"I am sure we have plenty of players who can cover it (the injuries) and we don't miss them too much," Moyes said.
"We want to play well. We've not done as well in the league as we should have. We want to put it right."
Since October 1999, United have lost just once to Villa in 33 matches – that defeat coming in December 2009 when Gabril Agbonlahor's header gave the Birmingham outfit a 1-0 win at Old Trafford.
The match will be the 500th club appearance of Wayne Rooney's career and he is currently on 149 Premier League goals for Manchester United.
Without last season's top-scorer Van Persie, who scored a hat-trick against Villa when the two sides met at Old Trafford in April, Rooney will be asked to lead the line up front and is in good form domestically, scoring three in as many matches.
They have won just seven points at Villa Park – only Sunderland have earned fewer at home in the Premier League – and scored just six goals at the venue in seven matches.
Despite having just 23 per cent possession at Southampton last week, they produced a great 3-2 win – a result that extended their unbeaten run to five.
Joe Bennett (back), Charles N'Zogbia (calf) and Jores Okore (knee) remain on Villa's injury list.
