Table-topping Manchester United visit rock-bottom Queens Park Rangers on Saturday in the Premier League, while defending champions Manchester City host Chelsea on Sunday.
Elsewhere this weekend, Arsenal will aim to ease their troubles against Aston Villa, Fulham and Stoke City meet in a lunchtime kick-off and Reading and Wigan Athletic are involved in a relegation six-pointer.
Sunderland travel to West Bromwich Albion, Norwich City welcome Everton and, on Sunday, Newcastle United boss Alan Pardew takes on former club Southampton in a vitally important game.
With Manchester City not in action until Sunday, Manchester United could open a 15-point lead at the top of the table come the end of Saturday when they take on QPR. Sir Alex Ferguson's club will visit Loftus Road in fine form and they will also know they have only dropped two points in Premier League history against QPR. Harry Redknapp will therefore be fully aware of the task he faces in an attempt to close the seven-point gap to safety for his relegation-threatened side.
Manchester City will continue their attempt to cling to the tails of derby rivals Manchester United when Roberto Mancini's side welcome Chelsea in Sunday's lunchtime kick-off live on Sky Sports HD1 and 3D. The defending champions seem to be fighting a losing battle to keep their trophy and it will be a difficult job this weekend. Chelsea, who have lost only one of the last four Premier League meetings with City, are themselves not certain of a place in the top four and so interim boss Rafa Benitez will be desperate for a win to ease some of the criticism he has been receiving.
Also on Sunday, Pardew's Newcastle host his former club, Southampton, in what is a crucial game at the bottom of the table. Neither side are safe from relegation, with Newcastle in 16th position and Southampton one place above. Both Pardew and his opposite number, Mauricio Pochettino, can as a result afford no slip ups. But Newcastle can be confident after losing none of their last eight Premier League home games against Southampton.
Under-fire Arsenal boss Arsene Wenger was dealt another setback on Tuesday when his side were convincingly beaten by Bayern Munich in the UEFA Champions League. That has left the Emirates Stadium club's hopes of winning a trophy seemingly in tatters for yet another season. And, in the wake of last weekend's FA Cup humiliation by Blackburn Rovers, Wenger will know anything less than a home win against a relegation-fighting Aston Villa on Saturday would cause trouble.
Reading and Wigan both occupy the relegation zone and games are running out, with just 12 remaining in the season. A win for either respective boss Brian McDermott or Roberto Martinez could as a result be a huge step towards survival while delivering a crushing blow to their rivals. The clubs also know each other well having played fixtures in each of England's four divisions.
Stoke City will continue their quest to record the highest Premier League finish in their history when they travel to Craven Cottage to take on Fulham, with all the action live on Sky Sports HD2 on Saturday lunchtime. Tony Pulis' squad earned just their first win of 2013 when defeating Reading last time out but they remain in the top half of the table and are hoping to stay there. However, Fulham will not be easy opponents, despite struggling for form, and the last four Premier League clashes between the London club and Stoke have ended in home wins.
The statistics suggest there could be a goal-fest at The Hawthorns when West Brom take on Martin O'Neill's Sunderland, with each of the last four top-flight meetings averaging more than 3.5 goals. Steve Clarke's West Brom earned just a first win in seven games when hitting Liverpool with a smash-and-grab victory at Anfield in their lasting outing and he will hope more of the same against a Sunderland side who have lost back-to-back league games against Reading and Arsenal.
Saturday also sees Everton travel to Norwich City, where David Moyes will want his visitors to earn what would be just a second win in six games. The Goodison Park club's season is in danger of fizzling out and there have been suggestions Moyes could leave in the summer. The Scot will therefore want to have full focus on the game. Norwich, though, are only six points from the relegation zone and will be wary of getting dragged into danger.