The man who took Mane's place in the side, albeit with a change of formation, Nottingham Forest's Cheikhou Kouyate, was stretchered off in their defeat to the Netherlands in their group opener.
The Senegalese FA have since came out and confirmed he will miss this tie with muscle inflammation, meaning they could revert back to a 4-2-3-1 shape against weaker opposition.
Better news for Aliou Cisse is that Abdou Diallo's injury is not as serious as first feared after he also went off on Monday.
Diallo returned to training on Wednesday after it was revealed that he was substituted because of muscle cramps.
That is a relief for Cisse, because Diallo was already covering at left-back for the injured AC Milan man Fode Ballo-Toure, who remains out.
Edouard Mendy's position in the side is now in doubt following his two howlers against Holland, with Seny Dieng and Alfred Gomis both capable deputies for the out-of-form Chelsea goalkeeper.
Senegal looked good on the ball and in attack in that defeat, but lacked a presence up front.
Boulaye Dia started as the number nine but he has flattered to deceive for his country despite good form for Villarreal and Salernitana of late.
Famara Diedhiou was their top scorer in qualifying but has had injury troubles this season, and Bamba Dieng has been lacking minutes after a transfer to Nice fell through in the summer, so Dia will probably start again up front.
It was a surprise that Habib Diallo was left out of the squad despite great goalscoring form in Ligue 1 for Strasbourg, while another attacking option, Keita Balde, is currently serving a drugs ban after a peculiar transfer to Spartak Moscow in the summer.
The solution could be to revert back to the 4-2-3-1 which has served them well previously, and Kouyate's injury could make Cisse's mind up for him, with Nicolas Jackson and Iliman Ndiaye other options to come in.
Senegal possible starting lineup:
Dieng; Sabaly, Koulibaly, Cisse, Diallo; I Gueye, N Mendy; Ndiaye, I Sarr, Diatta, Dia
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