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.
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.