With leaders Arsenal not in action until Monday, and second-placed Manchester United playing on Sunday, most of the attention on Saturday will be focused on the wrong end of the table.
Fulham, fresh from their win over Aston Villa last weekend, are now just three points clear of safety and will look to maintain their momentum by winning at fellow-strugglers Middlesbrough.
With Jimmy Bullard, who scored the winner against Villa, and striker Brian McBride now both back to fitness after long-term injuries, manager Roy Hodgson believes things are looking up for his side.
"Both had injuries that lesser players might have looked at and thought 'This is going to take such a long time to come back from have I got the enthusiasm and strength of character to come back again and play at the highest level?'," Hodgson said.
"Both of them set their stalls out to do that and both succeeded very well.
"(The win over Villa) is a step in the right direction, but there's still a lot to do. It's a start, but there's an awful long way to go."
Birmingham, who occupy the third relegation spot, are away to West Ham United, while Reading, just a point above the relegation zone and on a run of six straight defeats, face a tough trip to Everton.
Sunderland, just two points above the bottom three, entertain Wigan, hoping to maintain a strong home record that has seen them win six and draw three of their 12 games.
"Our destiny is in our own hands and its a good position to be in, not to rely on anyone else, Sunderland captain Dean Whitehead said.
"If we do our jobs properly we'll be fine. There is no reason why we cant push up the table and start to look at the middle rather than the bottom. We haven't set any points targets, we just want to get as many as we can."
Come Sunday, though, the focus will switch to Old Trafford and Stamford Bridge, where Manchester United and Chelsea will bid to close the gap on Arsenal, who host Blackburn Rovers on Monday.
United play neighbours and rivals Manchester City in a match that is sure to be overshadowed by tributes to commemorate the 50th anniversary of the Munich air disaster, in which 23 people, including eight United players, died in 1958.
The match is United's closest to the actual date, February 6, and the home club will hope that City fans respect their tributes.
At Stamford Bridge, Chelsea, four points behind United in third, take on a Liverpool side fresh from their first win in five league games last weekend.
Chelsea will again be without Didier Drogba, who is on international duty, while Liverpool had a scare when their leading scorer, Fernando Torres, came off after 23 minutes of Spain's friendly against France on Wednesday.
However, the Spaniard assured Liverpool fans he would be fit to play, having scored against Chelsea earlier in the season.
"I preferred not to risk it. I demanded the change," Torres said of his decision to go off. "I will have medical tests, but I intend to play on Sunday against Chelsea."
Aston Villa take on Newcastle United, Bolton Wanderers face Portsmouth and bottom side Derby County welcome Tottenham Hotspur in Saturday's other games.