The left-back had been earmarked for a shock return to Fratton Park next month following knee surgery.
However, Holmes-Dennis has suffered a training setback and this week underwent an exploratory operation.
The focus is once again on the knee he damaged 39 minutes into his Blues debut on the opening day of the season.
It means the 22-year-old is no longer likely to feature for Pompey during the remaining period of his season-long loan spell.
For Kenny Jackett it’s a blow, having previously spoken how he was looking forward to having Holmes-Dennis back.
He told The News: ‘Holmes-Dennis had an exploratory operation in the week and is unlikely to return to us.
‘He was working at Huddersfield very hard and felt problems with his knee.
‘The surgeon very quickly decided he needed to do an exploratory operation.
‘However, I don’t know what the results of those are.
‘We were hopeful, he was targeting an April return, but that is very unlikely now.
‘It is a shame, but Tareiq has got to keep working away.
‘You have these setbacks and, if it puts him back a month, he has to double his determination to get back into it.’
The Holmes-Dennis blow arrived in a week when Pompey have received a double injury boost.
Stuart O’Keefe (groin) and Oli Hawkins (hamstring) are back in training following absences and in the frame for tomorrow’s visit to Walsall.
O’Keefe has not featured since mid-December, while Hawkins has been sidelined for the past three matches.
They join recent returnees Brett Pitman and Gareth Evans.
Stephen Henderson has long since returned to Nottingham Forest rehabilitation on a thigh problem.
That leaves Danny Rose as Pompey’s remaining casualty as he progresses following a broken leg.
According to Jackett, the midfielder is ahead of schedule in his ongoing rehabilitation.
Although it is still anticipated he will be sidelined for the remainder of the season.
He added: ‘Danny is doing well, as you would expect, doing everything competently, conscientiously and ahead of schedule.
‘Our expectations are pre-season for him.’