FA Cup holders Chelsea will be without captain John Terry and left-back Ashley Cole when they face Championship promotion chasers Cardiff City at Stamford Bridge on Saturday.
Chelsea manager Carlo Ancelotti has allowed Terry time off to sort out some personal problems, while Cole will be out for three months after breaking an ankle against Everton on Wednesday.
Cardiff, beaten FA Cup finalists two seasons ago, travel with limited options as captain Mark Hudson, Joe Ledley, Stephen McPhail, Miguel Comminges, Josh Magennis, Kelvin Etuhu and Tony Capaldi are all unavailable due to injury or ineligibility, while striker Jay Bothroyd (ankle) and midfielder Gavin Rae (hamstring) are doubtful.
Bolton Wanderers switch their focus from battling to stay in the Premier League to their clash with Tottenham Hotspur at the Reebok Stadium on Sunday without Gary Cahill.
The defender will be out for the forseeable future after developing a blood clot in his arm which required specialist emergency treatment last week. They will also be without Vladimir Weiss and Jack Wilshere who are cup-tied.
Spurs will again be without winger Aaron Lennon and manager Harry Redknapp is likely to reshuffle his side following a 1-0 defeat at Wolverhampton Wanderers on Wednesday.
Skipper Michael Dawson will have a late test on an ankle, while Ledley King and Luca Modric are also doubts.
Manchester City should have Wayne Bridge in the side to meet Premier League rivals Stoke City at Eastlands on Saturday.
Bridge returned for last week's shock 2-1 defeat at Hull City after missing the previous 12 games with a knee injury. Kolo Toure should also be fit after taking a knock in the match against Bolton on Tuesday.
Stoke manager Tony Pulis, whose side scored a well-deserved win over Arsenal in the fourth round, said his men must go to Eastlands with a positive mentality.
"I am looking to pick a positive team and go there to have a right go," he said.
Portsmouth will be aiming to put all their financial and off-field worries behind them for at least a few hours when they make the short trip along the south coast to face arch-rivals Southampton, currently mid-table in League One.
Portsmouth, FA Cup winners two years ago but now battling for their very existence in the courts because of their financial problems, will be looking for their first win at St Mary's and their first FA Cup win against Southampton after four defeats since their first meeting in 1905-06.
Aston Villa, chasing a first FA Cup success since 1957, travel to Championship side Crystal Palace with doubts over Stilian Petrov (ankle) and top scorer Gabriel Agbonlahor (leg injury).
Birmingham
