The intense pressure on the unpopular Rovers manager Steve Kean has been compounded by fan groups and local media calling for his resignation, while Owen Coyle's Bolton go into Tuesday night's match at Blackburn, just 11 miles down the road, on the back of five consecutive losses.
Bolton, who are bottom, have won only three of their 16 league matches and have only nine points while Rovers are just one point and one place above them on 10.
"Stick with us. With a game that is as important as this, stick with us," Kean pleaded to Rovers fans on Monday despite their regular demands for his sacking all season.
At the more glamorous end of the table, leaders Manchester City, whose win over Arsenal on Sunday took them to 41 points, are at home to Stoke City hoping to extend their lead over their Manchester rivals, who are two points behind.
United beat Queens Park Rangers 2-0 on Sunday to briefly dislodge City from top spot and Sir Alex Ferguson's men return to London on Wednesday to face erratic Fulham.
Another intriguing battle sees third-placed Tottenham Hotspur face fourth-placed Chelsea at White Hart Lane. Spurs have the chance of opening up a five point lead, with a game in hand, over their London rivals.
Bolton manager Coyle believes the clash with Blackburn is "probably the biggest game of the season for both clubs."
"We have to make sure that we're ready to be on the front foot and be really positive and go and win the game," he told reporters.
The position of Rovers manager Kean was further undermined by a local newspaper publicly calling for the Blackburn board to sack the Scot on Monday, a highly unusual move by local press usually supportive of its League club.
As the Rovers board is set to meet on Wednesday, speculation suggests a loss to Bolton could spell the end of Kean's year-long tenure.
After a pulsating 1-0 victory against Arsenal, Manchester City manager Roberto Mancini said home form will be vital to wrestle the title away from United.
A win against Stoke, who visit the Etihad Stadium after four wins in a row, would see City preserve their 100 percent home record in the league and keep them top at Christmas for the first time since 1929.
Spurs take on Chelsea hoping Gareth Bale's sprained ankle and Jermain Defoe's hamstring problems will heal in time. Winger Aaron Lennon is out after he tore a hamstring during the 1-0 win against Sunderland on Sunday.
Chelsea captain John Terry is an injury worry for the visitors and manager Andre Villas-Boas will hope a return to training for David Luiz and Ramires following Saturday's disappointing 1-1 draw at Wigan Athletic will see them fit for the match.
Although Manchester City virtually extinguished Arsenal's title ambitions on Sunday according to manager Arsene Wenger, the Londoners, in fifth place, are not out of the race for a Champions League spot and visit stuttering Aston Villa on Wednesday.
