The hosts scored three goals in the opening eight minutes, through Alkhaly Bangoura in the 2nd minute, and a brace from Amine Chermiti in the 2nd and 8th minute, as it ended 3 - 0 in favour of the hosts at half time.
Etoile resumed the second half with the same intensity and scored their fourth through Aymen Sfaxi in the 54th minute.
Plateau United responded with two late away goals, the first in the 70th minute when Rapheal Ayagwa converted a penalty and Obolaye scored the second in the 82nd minute.
Kennedy Boboye's side had earlier defeated Eding Sports and 1 - 0 in the second leg to progress to the next round.
Other Nigerian representatives on the continent will be in action on Wednesday, March 7
The result means that Plateau United will have to win by a margin of two goals to progress to the money spinning group stage of the CAF Champions League.
Plateau United will host Etoile du Sahel in the return fixture on Friday, March 16.
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