Jose Mourinho's men are in action first this weekend as they travel to Hull City as the reverse fixtures from the opening weekend of the season take place, knowing victory at the KC Stadium will put them top of the pile.
Manchester City face a testing trip to Newcastle United on Sunday, where three points will lift them to the pinnacle, while Arsenal must wait until Monday evening for their meeting with opening day conquerors Aston Villa, with both matches live on Sky Sports 1HD.
There is a key relegation clash in south Wales as West Ham tackle Cardiff City and another in west London where struggling Fulham welcome bottom club Sunderland.
A feeling of deja vu will pervade around Old Trafford as Swansea, fresh from their FA Cup victory over the reigning champions, take on Manchester United once again on Saturday Night Football.
Top-four hopefuls Tottenham have a home London derby against Crystal Palace, Everton host Norwich and Liverpool make the trip to Stoke, with the latter fixture also live on Sky Sports 1HD, while Southampton meet West Brom.
Chelsea's flawless form over the festive period has put them within striking distance of the Premier League summit and they can climb into top spot, temporarily at least, with victory over Hull City at the KC Stadium in Saturday's early game. Steve Bruce's side were beaten 2-0 at Stamford Bridge on the opening weekend, but have since proved their top-flight credentials - with a home success against Liverpool one notable highlight. Bruce does not have the best of managerial records against the Blues, with just one win, five draws and 12 defeats from his 18 meetings, and Hull have not beaten Chelsea in their nine showdowns since their last success in October 1988.
Manchester City have moved ominously towards top gear in recent weeks, with eight victories and one draw from their last nine Premier League games taking them to just one point behind Arsenal prior to Sunday's clash with Newcastle at St James' Park, live on Sky Sports 1HD. Manuel Pellegrini's men will end the weekend in first place with a victory, and have an outstanding recent record against the Magpies. Eight defeats in a row and no wins over their last 14 top-flight meetings makes this a game to dread for the Toon Army, while successive defeats against Arsenal and West Brom have seen them slip to eighth in the table.
Regardless of how their title rivals fare on Saturday and Sunday, Arsenal will retain their leadership with victory in the concluding fixture of the 21st round of matches, away to Aston Villa. Paul Lambert's men memorably triumphed 3-1 at Emirates Stadium back on the opening day, a defeat which caused much hand-wringing from the Gunners faithful but has since been consigned to history as they look to end a nine-year silverware drought. Christian Benteke scored twice that day, but the Belgium striker, so pivotal to Villa avoiding the drop last term, has not found the net since September 14 - a run of 12 matches without troubling the scorers.
West Ham's current woes appear to outweigh any of their top-flight rivals as they prepare for Saturday's vital trip to fellow strugglers Cardiff. Sam Allardyce's side have taken just two points from their last seven games to slide into the bottom three, were humbled 5-0 by Nottingham Forest in the FA Cup before being spanked 6-0 at Manchester City in the first leg of their Capital One Cup semi-final. Cardiff moved swiftly to bring in Ole Gunnar Solskjaer as Malky Mackay's replacement, with the Norwegian enjoying immediate success with an FA Cup win at Newcastle, but it is retaining their top-flight status which is his key concern, as they sit just one point above the bottom three.
Sunderland continue to prop up the Premier League table ahead of their trip to Fulham, another team who remain in the relegation dogfight despite two victories from their last three games. Gus Poyet's men enjoyed a memorable 2-1 victory over Manchester United in their Capital One Cup semi-final first leg, but the manager was quick to stress in the immediate aftermath that any day at Wembley would be tarnished should they be unable to improve their current league plight. The Black Cats are four points from safety and five adrift of the Craven Cottage club, who were 1-0 victors at the Stadium of Light in August when both clubs had different managers at the helm.
Manchester United and Swansea go head-to-head for the second time in seven days at Old Trafford with a swift reunion in the Premier League coming on the back of their FA Cup third round meeting. The Swans were shock 2-1 winners on Sunday, inflicting the second of three successive defeats on beleaguered Red Devils boss David Moyes, with their cup exit coming after a home defeat by Tottenham and prior to their League Cup setback at Sunderland. A fourth reverse in all competitions would surely render the champions' title defence dead in the water, with Arsenal already 11 points ahead, and pile further pressure onto Moyes' shoulders.
Liverpool led the Premier League on Christmas Day but now have six points to make up on Arsenal as they prepare to face Stoke City on Sunday afternoon, live on Sky Sports 1HD. The Britannia Stadium has not been a happy hunting ground for the Merseyside club, with three defeats in succession and no victories to show from their five Premier League meetings. The Potters are a different proposition under Mark Hughes than Tony Pulis, but their home form remains a key strength, with three victories from their last five, including against Chelsea. Luis Suarez has scored just one in his last four games, after an astonishing 10 in his previous four matches.
Crystal Palace face a testing London derby against Tottenham at White Hart Lane on Saturday with Pulis' new club just one point away from scrambling clear of the drop zone. On the opening day, when Andre Villas-Boas and Ian Holloway were the respective managers, Spurs claimed a 1-0 win courtesy of Roberto Soldado's penalty. Tim Sherwood is the new man in the White Hart Lane dugout and has overseen a run of 10 points from four games, including a famous triumph away to Manchester United, before Saturday's FA Cup exit at the hands of Arsenal. Palace are unbeaten at Spurs in the Premier League, with one win and three draws from their four visits.
Everton and Norwich meet at Goodison Park on Saturday with markedly differing ambitions for Roberto Martinez and Chris Hughton. The home side are just one point behind local rivals Liverpool in fourth and can move into the UEFA Champions League places for a period with the Reds not in action until Sunday. The Canaries, meanwhile, are among a clutch of clubs on the fringes of the relegation places, with only three points separating Hughton's men from the drop zone. The two teams drew 2-2 at Carrow Road back in August, a fourth draw in their last five top-flight meetings with Norwich claiming victory in the other.
Southampton take on West Brom at St Mary's eager to snap out of a slump which has seen them suffer six defeats in their last nine top-flight outings and slide down the Premier League table to ninth place. Manuel Pellegrini's men have had some testing matches in that spell, including Chelsea (twice), Arsenal, Manchester City, Tottenham, Everton and Newcastle, coupled with injuries to key players. West Brom appointed Pepe Mel on Thursday to replace the axed Steve Clarke, but caretaker boss Keith Downing will be in charge on Saturday. Downing has overseen a four-game unbeaten run, although three of those games were draws and the Baggies are only four points above the bottom three.