Mane left the Reds for Bayern Munich over the summer.
Jurgen Klopp's side have struggled to get up and running in every competition so far and Wenger has highlighted the fact Darwin Nunez is yet to settle in the side and there's a Mane-shaped hole in the squad.
"It's difficult to understand," he told beIN Sports. "They have the same core (group of players), same type of game.
"They are less efficient in winning the ball back than before. Nunez, at the moment, hasn't worked out for them and they made a big investment. He's sitting on the bench.
"They lost Mane, who was a top level, big game player. He had something (about him), aggressive attitude and determination. He'd score no matter what happens, he'd make things happen.
"It's difficult to measure how much (his departure) takes away. They miss something they had before.