Gerry Dulac of the Pittsburgh Post-Gazette cited a source in reporting that Spence will miss the season with multiple ligament tears in his left knee.
The team's third-round draft pick was hurt during the third quarter of Thursday night's preseason finale against the Carolina Panthers.
The loss of Spence causes problems for the Steelers in the middle of their defense, where he projected as a primary backup. Linebacker Stevenson Sylvester also is out of the picture as he mends from a medial collateral ligament injury.
The Steelers will plug veteran Brandon Johnson in Spence's spot after he spent the past four seasons with the Cincinnati Bengals. Pittsburgh also should get James Harrison back for the regular season, but we expect to see his snap count reduced early in the season. Jason Worilds also was cleared to play this week, adding support on the outside and easing the pain of losing Spence.
The Steelers have been hit hard with injuries in recent weeks, but few teams navigate this type of chaos as well as Pittsburgh, an organization that's rarely caught blinking.
Follow Marc Sessler on Twitter @MarcSesslerNFL.