Watson, who caught 29 passes for 620 yards and two touchdowns in the regular season, suffered a knee injury in Sunday's loss to the Chicago Bears.
Media reports said that Watson had torn an ACL knee ligament and at a media conference on Monday, coach Matt LaFleur confirmed the receiver was out.
"Yeah, it's not good. So he'll be out for the season," he said.
"It's a big time loss. Just his presence on the field alone. He's so versatile in his ability to play multiple positions.
"Obviously, he's got an element in terms of his size and speed that's tough to replicate. There's not many built like him around the league. And I just I hurt for him, I obviously hurt for our team. But I also I just more for him," he said.
Quarterback Jordan Love was also replaced in Sunday's game with an elbow injury and his back-up Malik Willis was shaken up but LaFleur said they should be fine.
“I talked to both of those guys. They seem to be doing alright," he said.
"But as far as their limits (in practice) — I think they’re going to be OK, but we’ll find out over the next two days," he said.
