Both Hermann Hreidarsson and Danny Webber face at least six months out of action, after picking up serious injuries during the 2-0 defeat to Tottenham on Saturday.
A scan on Tuesday revealed that striker Webber suffered a ruptured anterior cruciate ligament and will see a specialist in London next week ahead of surgery.
Defender Hreidarsson ruptured an Achilles in the same game and will have surgery in London next week, with the news that both will be out for half a year dealing a bitter blow to struggling Pompey.
