Marcus Harness and Lee Brown have been ruled out of the south-coast derby.
Kenny Jackett expects the injured pair to return to training next week – but not in time to be considered for the Carabao Cup clash with Southampton.
The in-form Harness has been sidelined since straining a thigh at Blackpool last month.
Meanwhile, Brown has missed the past four matches with the Achilles problem sustained in the first-half against Coventry.
Pompey’s boss believes the duo have now run out of time to declare their availability for the September 24 visit of Southampton.
Instead he is pencilling in returns for the visit of struggling Bolton to Fratton Park on September 28.
And that deprives the Blues of their first-team presence for the eagerly-anticipated encounter with their Premier League neighbours.
Jackett said: ‘I doubt they’ll be ready for Southampton.
‘Maybe Harness will be back in training the Monday before, he’ll be back before Brown, but for matches it will be more like Saturday week (Bolton).
‘If Marcus is training a week today, then I'll give him a full week, usually I always prefer that when it’s a muscle injury.
‘We’ll see, if he surprises me that will be great, maybe he’ll come back Thursday-ish this week. Even so, he still needs a full week.
‘I would suggest it is lending itself towards Bolton for Marcus, at the moment.’
In Brown’s absence, Brandon Haunstrup has thrived as left-back deputy.
Certainly the youngster from Waterlooville will relish the opportunity to face Southampton at Fratton Park.
Haunstrup will once again feature in Pompey’s defence for Tuesday night’s League One fixture with Burton.
In addition, there are forthcoming matches against Wycombe (September 21) and Southampton.
In terms of replacing Harness, that is not quite so clear cut, with Gareth Evans and Ryan Williams in the running following injury.
Jackett added: ‘Somewhere during the course of next week, I am hoping Brown will also be back.
‘I would love them both back, Harness will be back before Brown, but Southampton might be a bit soon for the pair of them.’