Smith, the Boilermakers' top receiver, left Saturday's 31-21 win over Western Illinois in the fourth quarter with an injured right knee. He caught six passes for 43 yards before leaving the game.
Smith is scheduled to undergo tests in the next couple of days.
Smith caught 91 passes for 1,100 yards last season and was Robert Marve's top target with 12 catches against Notre Dame in the season opener. After leaving the game, he returned to the sideline on crutches with his right knee wrapped.
Information from ESPN.com's Adam Rittenberg and The Associated Press contributed to this report.