Former Barca boss Gerardo Martino experimented with playing Messi in a wider role when the two sides met in the Champions League last season, while the Argentine was deployed in a deeper central position during the thrashing of Elche at the weekend.
And Simeone claims the 27-year-old will only have a true impact on the Copa del Rey second-leg clash against Atleti if he is started away from a more congested central area of the pitch.
"Barcelona, historically, have a style of play they don't like to change," Simeone told a press conference. "In the last few games they've moved Messi to the right and put [Luis] Suarez through the middle. I think Neymar feels more comfortable on the left.
"If they want to play well, they need Messi on the right, and I think they will."
Simeone believes the game is different to their victory in the Champions League last term and has urged his players to fight in every minute of the game on Wednesday.
"We have to live every minute as if it were the last of the game, and in that manner we can achieve more than our objective," he said.
"The Champions League game at the Calderon was different. The atmosphere will be great, as it always is for these games. The fans don't need to add any more than they usually do.
"We expect a usual home game tomorrow, taking the game where it suits us. Tomorrow, we'll see if we can do it."
Simeone, who revealed he will make a decision on the fitness of Koke after training on Tuesday, had no comment to make on Cristiano Ronaldo's red card against Cordoba at the weekend.
"I've no opinion on Ronaldo. The committee will resolve it, they usually do it well," he added.