Neraysho Kasanwirjo has suffered a "long-term injury" Philippe Clement has confirmed.
The 22-year-old injured himself after coming on as a substitute for the Netherlands Under-21s over the international break in a match against England.
Kasanwirjo will meet with a surgeon this afternoon as Rangers prepare to learn the extent of the setback.
However, Clement will now be without the versatile defender for the foreseeable future.
"Kasanwirjo is going to have an appointment with a surgeon today, and we will have more news over the weekend - for sure a longer-term injury," Clement said.
"A blow for everyone, especially for him. This is football, it is really hard as he was adapting really well."
Kasanwirjo, who joined Rangers from Feyenoord on a loan with the option to buy this summer, has impressed playing across the defence this season. He ended the 1-0 win over Hearts a fortnight ago at right-back having replaced James Tavernier shortly after the hour mark.
Having also played as a left-back and centre-back over the course of the last few months, Kasanwirjo has quickly become an important member of the Rangers squad. Fellow Dutch defender Robin Propper has only featured sporadically in recent weeks while Ridvan Yilmaz is yet to feature after sustaining an injury in August.
Meanwhile, Nice are set to be missing both of their international full backs for their match against Rangers in the Europa League next week.
Rangers travel to France for their latest game in the competition after an encouraging start with the Ibrox side in tenth place in the table from 32 teams after two wins, a draw and a defeat so far.
And they will take encouragement from the fact that Nice have been rocked with injuries to key players during the international break.
France international right back Jonathan Clauss picked up a thigh injury while training with his national team during France's Nations League games against Israel and Italy.
And he will be joined on the sidelines by Tunisian international left-back Ali Abdi, who was injured during his country's African Cup of Nations game against Gambia.
The defensive duo at 32 and 30 are two of the most experienced players at Nice and their absence will be a bitter blow to manager Franck Haise.
Nice are also without long-term injury victims Nigerian international striker Terem Moffi, midfielder Morgan Sanson and Algerian international midfielder Hicham Boudaoui for the visit of Philippe Clement's men.
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