With only the top eight teams to advance to the knockout stage, Qatar's Al Gharafa sits in seventh on three points while Iran's Persepolis is two adrift in 10th spot.
Al Gharafa's impressive 4-2 win against Al Ain of the UAE was undone by its 2-1 defeat to Al Wasl on Matchday Three and the Qatar side has to bounce back if it is to stay on track for the next stage.
The records, however, are against the team as Al Gharafa has lost its last four away matches (including neutral venues) on the continental stage.
Persepolis will be equally desperate to revive its campaign, with the two-time AFC Champions League runner-up still seeking its first win of the season.
The 1-0 defeat to Qatar's Al Sadd SC on Matchday Three extended its winless run on the continent to six games, its longest stretch ever without a victory.