The Buccaneers are making their continental return after a five-year hiatus, having falling short in the Champions League final to record eight-time champions Al Ahly in 2013.
Their first test is against Seychelles outfit Light Stars FC, who will be making their debut in the competition after previously competing in the Confederation Cup in 2016.
Pirates were without Motshwari in their second successive Soweto Derby this season as they cruised past Kaizer Chiefs to advance to the Telkom Knockout final last Saturday.
The 27-year-old, who has been a key figure in central midfield for the Bucs, picked up a knock in a friendly fixture during the international break, and is hurriedly working his way back.
"The [Pirates] medical team has been treating the player for his injury and will further monitor his progress over the next two days before they clear him for the match against Light Stars FC," read a statement on the club's website.
Meanwhile, winger Luvuyo Memela, who underwent surgery on an injured knee at the end of last season, suffered another setback last month and continues his recovery, with defender Gladwin Shitolo also pushing for a return.
"Memela, who is recovering from a long-term injury, continues to undergo rehabilitation. Amigo, as he is affectionately known, has started his first phase of strength work combined with work on the treadmill as well as aqua training," said the club.
"Another player nearing full recovery is defender Gladwin Shitolo who is recovering from a torn quad muscle. He has passed his functional tests and will now start with his strengthening programme."
According to the statement, also ruled out of Wednesday evening's tie are Brilliant Khuzwayo and Ntsikilelo Nyauza, who are nursing ankle ailments, and Mthokozise Dube with a hamstring injury.