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The Mauve and Yellow discovered the opponents in the continental competition during Tuesday’s draw at the CAF headquarters in Cairo, Egypt.
Medeama will be playing in the Champions League for the first time in the club’s history after winning the Ghana Premier League last season.
Evans Adotey’s side would, however, be counting on their past experience in Africa, having featured in the CAF Confederations Cup twice in the last decade.
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Their opponents, Remo Stars, finished second in the Nigeria Professional Football League champions and are one of the fast-rising teams in West Africa.
The first leg of the Champions League tie will be hosted at Cape Coast Stadium on the weekend of 18-20 August.
Remo Stars will then host Medeama in the second leg in Nigeria a week later on 25 - 27 August, with the winner advancing to the second preliminary round.
Meanwhile, Ghana’s FA Cup winners Dreams FC have also been paired against Guinean side Milo FC de Kankan in the first preliminary round of the CAF Confederation Cup.
The first preliminary round is fixed for the weekend of 18 - 20 August for the 1st leg matches and 25 - 27 August for the 2nd leg ties.