Ayew, who is Ghana's all-time leading appearance holder, linked up with his national side ahead of two Africa Cup of Nations qualifiers against Angola.
The 33-year-old did not feature in the matchday squad for Thursday's 1-0 over Angola thanks to a 96th-minute winner from Bournemouth's Antoine Semenyo.
Prior to Monday's 1-1 draw against the same opponents, the Ghana football association confirmed that Ayew has returned to Forest after picking up a knee injury in bizarre circumstances.
A statement read: "Ghana captain Andre Ayew has been ruled out of the Africa Cup of Nations qualifier against Angola after sustaining a knee injury on Thursday."
"Ayew slipped on his way to the dressing room and hurt his knee as findings of the MRI scan have meant that he has to return to his club for further treatment."
The experienced forward joined Forest in February on a deal until the end of the season following his departure from Qatari side Al-Sadd.
Ayew has failed to score in his seven appearances for the East Midlands club, but a potential spell on the sidelines would still come as a blow to Forest, who have also have fitness doubts over Chris Wood and Brennan Johnson.
Wood suffered a thigh injury during a 3-1 defeat to Tottenham earlier this month, but he still travelled to New Zealand for two friendlies against China.
However, Wood was unable to feature in Thursday's goalless draw, and he was sent back to Forest for further assessment prior to Sunday's fixture.
Commenting on the situation, New Zealand interim coach Darren Bazeley told reporters: "We've been monitoring Chris ever since he arrived but he didn't travel with the team yesterday, he stayed in Auckland for some consultation. Between the two medical departments, we feel it's in the best interests of Chris to return home, to get back to his club and to monitor and evaluate the injury by his own club.
"Chris is not a player you take risks with. He did come with the full intention of playing. You know Chris, he wants to play every game. We trained but it just wasn't quite right so we've taken the advice and the best thing for Chris now is to get back and make sure he's in a good place when he gets home."
Johnson, meanwhile, was unable to report for international duty due to a groin problem that he picked up earlier this month and the way his injury was handled frustrated Wales boss Rob Page.
Forest manager Steve Cooper will be hoping that Ayew, Wood and Johnson can return to action as soon as possible, with the Reds involved in a relegation fight.
They are currently just two points clear of the drop zone ahead of Saturday's home meeting with Wolverhampton Wanderers.