Manyama faces a long lay-off after he goes under the knife to repair a damaged ligament in his knee this week.
The former PSL Footballer of the Year has had a turbulent stay at Naturena since his arrival from Turkey at the start of the season, having earlier survived a serious car accident.
The 28-year-old missed six weeks of the season after injuring his elbow during a horrific crash in October and has once again been derailed for up to three months with a knee injury picked up against AmaZulu last week.
“Lebogang Manyama has a torn knee ligament. He will undergo surgery on Wednesday. He is expected to resume training in two to three months,” revealed Chiefs' physiotherapist Dave Milner on the club's website.
Meanwhile, the club have also provided an update on several other key players in the medical treatment room, including skipper Itumeleng Khune.
"Goalkeeper Itumeleng Khune has begun gym work after a shoulder surgery. The skipper is expected to return to action during next season’s pre-season," read the statement.
"Recovering from an ankle injury is Mulomowandau [Erick] Mathoho. The medical report has revealed that the towering defender will remain on the sidelines for a month before resuming training.
"Philani Zulu is also on the comeback trail. Zulu aggravated his facial fracture in the CAF Confederation Cup encounter against Madagascar’s Elgeco Plus. The midfielder has been a regular feature since coach Ernst Middendorp took charge in December.
"Further good news is the progress made by Joseph Molangoane. The midfield dynamo is making a steady return from a long-term ankle injury. Molangoane has started non-contact training and should begin full training in two to three weeks."
Bafana Bafana defender Ramahlwe Mphahlele is expected to make a retun this weekend after being cleared by the medical team following a knee injury.
The 28-year-old right-back last featured against Golden Arrows on December 1, and made an appearance with the reserve side against AmaZulu on the weekend.
Chiefs next face ABC Motsepe League side Tornado FC in the Nedbank Cup last-32 in Mdantsane on Sunday, following their Confederation Cup exit at the hands of ZESCO United.