Liverpool's bid for a first English title since 1990 was revitalised by last weekend's win over Chelsea.
But Reds boss Rafael Benitez faces a test of his squad's strength in depth as he seeks to keep the momentum going at Portsmouth on Saturday, less than 72 hours after a gruelling, extra-time FA Cup defeat by Everton.
With Manchester United not in action until Sunday's trip to in-form West Ham, Benitez's men can return to the top of the table — temporarily at least — by taking all three points at Fratton Park.
But the required victory will have to be secured without influential skipper Steven Gerrard, who tore a hamstring muscle early in the Everton defeat and is facing a three-week lay-off at least.
Benitez may also feel that star striker Fernando Torres, who looked distinctly weary in that match, may not be up to a third start in the space of seven days, a situation which will inevitably raise further questions about the wisdom of selling Robbie Keane back to Tottenham this week.
Portsmouth, with just two wins in 15 matches since Tony Adams took over as manager, are hoping for a boost from the arrival of Greek duo Angelos Basinas – who arrived in a deadline-day switch from AEK Athens – and Theofanis Gekas, on loan from Bayer Leverkusen.
First-team coach Johnny Metgod is backing the pair to lift the gloom around the club.
"Gekas has got a very good goalscoring record, not only in Greece but in Germany, and Basinas is a very clever, intelligent midfield player," Metgod reported.
Chelsea welcome back key defender Ricardo Carvalho from injury as they attempt to put their title bid back on track at home to Hull, and the Portugal centreback believes the Blues will also get a boost from the involvement of his international team-mate Ricardo Quaresma.
The winger has been signed on loan from Inter Milan and Carvalho is backing him to provide the imaginative spark Chelsea have lacked of late.
"Quaresma is a very fast and explosive player who is a real warrior on the pitch, so he will be able to handle the physical nature of the Premier League," Carvalho said.
"At the same time he is a very technical player and can score goals, which will be good for us. He will be a huge help to us at this time of the season."
"He will add more pace, which is important. Nicolas Anelka and Didier Drogba will love playing with him because he gets a lot of assists.
"We have to be strong between now and the end of the season after the defeat to Liverpool and I just want to get back to help out."
A 2-2 draw with bottom side West Brom enabled Hull to halt a run of six successive defeats last weekend but Phil Brown's squad have since lost striker Daniel Cousin and midfielder Jimmy Bullard to injuries.
Any slip-ups from Chelsea could see Aston Villa move into third place provided Martin O'Neill's side extend their run of away victories to a club record seven at the expense of relegation-threatened Blackburn.
Keane's second debut for Tottenham will come against north London rivals Arsenal tomorrow in a derby that is critical to both Spurs' hopes of pulling away from the relegation zone and the Gunners bid for a return to the Champions League next season.
Tottenham Manager Harry Redknapp has signalled that Keane will be his first-choice striker by naming him as team captain, leaving Roman Pavlyuchenko and Darren Bent to battle for the second forward slot.
With the advantage of a game in hand over their nearest rivals, Manchester Untied are looking very well placed to claim another Premier League trophy.
That impression will be bolstered on Sunday as their recent injury woes ease with the anticipated return of Patrice Evra and Wayne Rooney from foot and hamstring injuries respectively.
Unbeaten in eight matches, West Ham could hand a debut to loan signing Radoslav Kovac, the experienced Czech Republic midfielder.
       
Saturday
Blackburn v Aston Villa, Chelsea v Hull, Everton v Bolton, Manchester City v Middlesbrough (2045), Portsmouth v Liverpool (0130 Sunday), Sunderland v Stoke City, West Brom v Newcastle, Wigan v Fulham
       
Sunday
Tottenham v Arsenal (2130 GMT), West Ham v Manchester Utd (midnight Monday)