Smith, being eased back into the rotation, played about a dozen snaps in the 10-9 loss to Carolina. He missed the previous five games while seeking treatment for substance abuse.
With Smith in his second week of practice, and with some game repetitions under his belt, San Francisco defensive coordinator Vic Fangio said Smith will see an increased role.
"He will play a lot," Fangio said.
Smith said after the Carolina game he was ready for an increased role. The 49ers will need him on the field as much as possible as they face Drew Brees. Smith has 34 sacks in 36 NFL games.
Fangio said the chances are good that standout rookie safety Eric Reid, who suffered his second concussion of the season in the Carolina game, plays against the Saints. He must pass the NFL's concussions protocol, but he is making progress.
Fangio said it is "iffy" that defensive tackle Ray McDonald plays. He has a high left ankle sprain. McDonald did not express optimism Wednesday that he will play in New Orleans. He is set to be replaced by Tony Jerod-Eddie, who has played well in a reserve role.
Like Reid, tight end Vernon Davis remains on course to play Sunday. He suffered a concussion Sunday.
Meanwhile, offensive coordinator Greg Roman said receiver Michael Crabtree is "progressing nicely" from a torn Achilles he suffered in May. He must be activated by Nov. 26. He didn't practice Wednesday, but the team said it was a built-in recovery day.