Lupul returned to the lineup Saturday after missing one game due to injury, but left after two periods. He has 22 goals and 44 points in 69 games this season.
"He is going to have surgery done on his knee," coach Randy Carlyle said. "It's a meniscus procedure and will be done arthroscopically. It will be three weeks to a month recovery."
The Maple Leafs, who begin a three-game road trip to end the regular season Tuesday at the Tampa Bay Lightning, are three points behind the Columbus Blue Jackets for the Eastern Conference's second wild-card spot in the Stanley Cup Playoffs. The Blue Jackets also hold a game in hand.