The Buccaneers host CS Sfaxian at Orlando Stadium tonight, having beaten the Tunisians 1-0 on the road last month courtesy of a brilliant Thabo Rakhale goal.
Another win tonight, coupled with a victory for Zamalek away to AC Leopards tomorrow, will see Pirates qualify for the last four.
However, a defeat could allow both Sfaxien and Leopards back into contention with two games remaining.
Zamalek, who knocked Kaizer Chiefs out the CA Champions League and who beat Pirates at home on 11 July, need only a draw to secure their spot in the semifinals.
Group B Fixtures
August 8: Orlando Pirates vs CS Sfaxien
August 9: AC Leopards vs Zamalek
Standings
Zamalek 9 (+4 goal-difference)
Orlando Pirates 6 (+1)
CS Sfaxien 1 (-2)
AC Leopards 1 (-3)