Ricardo Rocha and Luke Varney are struggling to make Pompey’s FA Cup re-match with Chelsea.
The duo have yet to return to training, having been sidelined by injury for the past few weeks.
And they remain doubts for Sunday’s fixture at Stamford Bridge between the 2010 FA Cup finalists.
Varney is still edging his way to fitness following a medial knee ligament strain.
He picked up the problem at Burnley and has missed the past four matches as a consequence.
The Blues’ joint-top goalscorer is making progress but Appleton is wary about aggravating the problem.
If he’s not ready, Varney won’t be risked for Chelsea, with the league programme the obvious priority.
As for Rocha, he is currently struggling with a calf problem.
The injury has kept him out of Pompey’s past two matches.
During that time, Aaron Mokoena and Greg Halford have had spells alongside Jason Pearce in the centre of defence.
But Rocha has been a first choice under Appleton and he’s produced some impressive displays.
The Chelsea fixture may well come too soon for the Portuguese 33-year-old as he looks to return.
Their continued absences will be partly offset by the returns of Halford and Joel Ward to the squad.
The pair are back in contention after serving their one-match suspensions.
Tal Ben Haim came in from the cold to take Halford’s right-back spot against Watford.
Meanwhile, Erik Huseklepp came into the Pompey side in place of the versatile Ward for that same match.
Their returns could also see veteran Kanu lose his place in the squad, after being on the bench for the Hornets’ visit.