England name their squad for the QBE Series on Wednesday morning with head coach Stuart Lancaster having to call up midfield and back row reinforcements.
Centres Manu Tuilagi and Brad Barritt have been ruled out of the Twickenham appointments with Australia, Argentina and New Zealand due to chest and foot injuries, while flanker Tom Croft is missing after undergoing knee surgery.
The replacements for Tuilagi and Barritt will provide the biggest talking point with two from Joel Tomkins, Luther Burrell, Jonathan Joseph and Henry Trinder set to join Billy Twelvetrees and Kyle Eastmond.
Leicester's Anthony Allen would have been an outsider for promotion from the Saxons squad but for the leg injury that has ruled him out for three months.
Of the quartet in contention, Burrell's inclusion is the most likely on the back of a dynamic start to the season that prompted Lancaster to last week describe the Northampton Saint as the Aviva Premiership's form centre.
Tomkins of Saracens is the favourite to join him in England's autumn squad, with Trinder a long shot given he would have to be promoted from outside the Saxons.
A midfield partnership of Twelvetrees and Burrell has had strong support to start against Australia on November 2, although that would mean Burrell switching from his more accustomed position of 12 to 13.
Lancaster spoke last week of the constraints of working within the agreement over player release between the Rugby Football Union and Premiership clubs and it is those rules that are likely to prevent him from replacing Croft with his preferred choice.
Number eights Sam Dickinson of Northampton and Dave Ewers of Exeter have excelled since Premiership action began in September but, like Trinder, are not in either senior squad named in August so are set to be rendered unavailable to Lancaster.
"Picking a player from outside the squads is a challenge. It can be achieved, but it's not been achieved yet," Lancaster said.
If Lancaster is unable to promote either Dickinson or Ewers, Tom Johnson of Exeter or Saracens' Will Fraser are in contention to fill the back row vacancy created by Croft's season-ending injury.
Selection for the series opener against the Wallabies is wide open in many positions with Toby Flood, who is competing with Owen Farrell and Freddie Burns at fly-half, among those anxious to make their mark.
"It's difficult. For me it's about playing well and managing my form at Leicester and then hopefully the decision is made in my favour," Leicester captain Flood told Sky Sports News.
"It's about getting as much as possible from the next few games.
"There is stiff competition at fly-half but that's also the case for hooker and the back row.
"There's some nice competition building up and the challenge is to get that shirt."