In a week where the managerial merry-go-round took several spins, Arsene Wenger - one of the Premier League's longest-serving bosses - will hope his youthful Arsenal side can bounce back from their first defeat of the season when they travel to Aston Villa.
The Premiership leaders' 3-1 reverse away to Sevilla in the Champions League on Tuesday ended Arsenal's 28-match unbeaten run.
Worse still was the hamstring injury sustained by Cesc Fabregas which looks likely to rule the Spanish international midfielder, who has scored 11 goals this season, out of the trip to Villa Park.
"We are very pessimistic for him, but he is still thinking he has a good chance," Wenger said of Fabregas.
"We will make a test tomorrow (Friday), we think he will be short for Saturday," added Wenger as he prepared his side to play a Villa team that beat Blackburn 4-0 on Wednesday.
Both club captain William Gallas and striker Emmanuel Adebayor are set to return after Wenger, conscious of Arsenal's busy December programme, rested the pair in midweek.
Victory would see Arsenal go six points clear of Manchester United ahead of their second-placed rivals' match against Fulham on Monday.
On the south coast, Portsmouth manager Harry Redknapp will look to end a week where he was arrested as part of an ongoing police probe into football corruption by guiding the high-flyers to victory over Everton.
Whatever the truth of the allegations surrounding him, the mere fact he's been questioned by police may have scuppered any hope the 60-year-old Redknapp had of replacing Steve McClaren as England coach.
Redknapp is likely to receive a hero's welcome at Fratton Park with Pompey seventh in the table. But the hosts face an Everton side which thrashed Sunderland 7-1 last time out.
Chelsea manager Avram Grant has been happy to let the club's results speak for themselves since he replaced the charismatic Jose Mourinho in the hotseat at Stamford Bridge.
The Blues, who thrashed Rosenborg 4-0 in the Champions League on Wednesday, have gone 13 games unbeaten since the Israeli took charge and head into Saturday's match with London rivals West Ham just five points off top spot.
"He is a little bit reserved and different to what they had. He has gone about his business quietly," said West Ham manager Alan Curbishley.
The Hammers, under the equally understated Curbishley, are unbeaten in six matches but their boss was under no illusions about the scale of the task facing his side.
"When you play a top-four team you need a few things going for you. You also need your players to all be on form, you cannot carry anyone."
Manchester City's rise to third in the table has been one of the most unexpected achievements of the season thus far, transforming both the club's reputation for self-inflicted wounds and reminding England fans of the ability of Sven-Goran Eriksson, whose spell in charge of the national side was marked by a series of controversies over his salary and private life, as a club coach.
The Swede's side are away to Wigan on Saturday in what will be Steve Bruce's first game in charge of the drop candidates since his arrival from Birmingham.
City's start to the season means that Eriksson doesn't plan to be spending too much more of Thai owner Thaksin Shinawatra's money during the January transfer window.
"It won't be like August when we took in eight players. It will be very few.
"We are not going to gamble. We have a good squad and a good base."
Brazil midfielder Elano has already been ruled out of the trip to the JJB Stadium with a hamstring injury.
Bottom-of-the-table Derby, under new boss Paul Jewell, are away to Sunderland who are sure to have been told a few home truths by boss Roy Keane.
Meanwhile struggling Middlesbrough are set to be without injured Australia goalkeeper Mark Schwarzer for their match with Reading.
Saturday's other match sees Blackburn at home to Newcastle with visiting manager Sam Allardyce facing criticism from some fans despite the north-east club's best start to a league season in 10 years.
Liverpool manager Rafael Benitez, whose side brought him some breathing space in his row with the club's American owners after their midweek Champions League success against Porto, takes the Reds on Sunday to Bolton, who will look to build on their surprise win over Manchester United.
Sunday's late kick-off match will sees Birmingham, in former Scotland coach Alex McLeish's first match in charge of the Blues, away to Tottenham with Manchester United at home to Fulham on Monday.

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