Ghana defender Nicholas is set to spend a long time in the treatment room after sustaining an injury on his return to pre-season training with club side Amiens.
The centre-back was diagnosed with a cruciate ligament rapture of the knee in France on Tuesday.
He will miss the start of the season, amid reports he will only return to action after the turn of the New Year.
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"He's a boy who went into [national duty] when he was already not in very good health, [he went] with an injured knee," Amiens manager Philippe Hinschberger told Le 11 Amienois.
"At least things are clear now, I think he aggravated the injury here too considering his situation.
"We have not in any way anticipated having to do a good part of the season without him."
Opoku's absence will be a massive blow for Amiens who are hoping to make another attempt to earn a return to the elite division.
Last term, the 23-year-old made 27 appearances in Ligue 2, starting in all the matches.
In the upcoming 2021-22 campaign, Amiens are billed to begin their promotion quest with a home clash with Auxerre later this month.
"I do not yet know enough about the level of players such as [Nathan] Monzango and [Valentin] Gendrey in playing a pivotal role in Ligue 2," Hinschberger added.
"But the club also has plans. In any case, there is a possibility that we will sign a defender.
"In the meantime, the problem is that we continue the preparation without [a lot of our defenders] since Emmanuel Lomotey also returned with a knock to the ischios, our right-back [Mickael Alphonse] is absent and we still do not have a left-back."
Opoku, who was recently on international duty as Ghana faced Morocco and Cote d'Ivoire in a double-header of friendlies, will likely be absent when the Black Stars assemble again for the start of the 2022 World Cup qualifiers.
In September, Ghana are set to take on Ethiopia and South Africa in back-to-back games on the road to Qatar 2022.
Should the defender remain in treatment until next year as highly speculated, he will likely miss the Africa Cup of Nations tournament in Cameroon.