Welker, who suffered a concussion in the Broncos' win over the Tennessee Titans earlier this month, practiced on a limited basis through the week, but he has not participated fully in a practice since the injury.
Broncos coach John Fox said Welker is still working through the league's concussion protocol and will make the trip with the team to the Bay Area.
"We didn't want to monkey around. Again, player safety is the key and we'll just rule him out for this game,'' Fox said following Friday's practice.
Because the Broncos have a bye in the wild-card weekend, Welker is expected to be ready for the team's first playoff game in the divisional round. Andre Caldwell again will work as the third wide receiver in Welker's absence, with Eric Decker or tight end Jacob Tamme working Welker's usual routes out of the slot.
Welker, who suffered a concussion just before halftime of the Broncos' Dec. 8 victory, had not practiced until Wednesday and has been held out of the last two games. Welker also suffered a concussion in the Broncos' Nov. 17 win over the Kansas City Chiefs.
Before he can play in a game, Welker would have to be declared symptom-free by both the Broncos' medical staff and a designated independent physician who has been approved by both the NFL and NFL Players Association.
Broncos defensive end Derek Wolfe also will not make this weekend's trip.
Wolfe took part on a limited basis in the Broncos' workout Wednesday. It was his first practice since suffering "seizure-like symptoms'' Nov. 29 on the team's bus ride to the airport in the days leading up to a Dec. 1 game in Kansas City. Wolfe missed Thursday's practice with the flu but practiced on a limited basis Friday.
Cornerback Kayvon Webster, who had surgery Dec. 13 to repair a fractured right thumb, practiced on a limited basis Friday and was listed as questionable for the game. Webster said he believes he is ready to play against the Raiders and into the postseason.
Backup center Steve Vallos, who suffered a concussion blocking on a kickoff return Sunday in Houston, did not practice this week and was also ruled out for Sunday's game.