The Swede was shown a straight red card in stoppage time after lunging at full-back Andres Guardado with his studs up in PSG's 2-1 victory in Spain on February 12.
Ibrahimovic will miss the return leg in Paris on March 6 and the first leg of the quarter-final should the French league leaders progress.
"I'm surprised by the decision," PSG coach Carlo Ancelotti said.
"I was already surprised when he was shown the red card. A two-game ban is incredible. I hope that UEFA will overturn the decision. We're going to appeal."
UEFA also rejected Schalke's protest that Galatasaray striker Didier Drogba was eligible to play in their first leg in Istanbul on February 20.
Ivorian striker Drogba joined the Turkish club in late January from Shanghai Shenhua. The Chinese club had initially tried to block the transfer saying he had violated the terms of his contract.
"Having examined all the documents of the case, the Control and Disciplinary Body decided to reject the protest lodged by Schalke," UEFA said in a statement.
