Leafs coach Mike Babcock confirmed at practice that Matthews will sit out the game as he continues to deal with an upper-body injury.
There was speculation that Matthews, who has 10 goals and nine assists in 16 games, might face the Devils after he returned to practice Wednesday.
Toronto has played well without its young star. The Maple Leafs have won four in a row, the past three victories coming without Matthews.
Nikita Soshnikov, recalled from the American Hockey League's Toronto Marlies earlier this week, will make his season debut in Matthews' place.