Westbrook fractured two ribs last week in Philadelphia's disheartening 23-17 loss Sunday. His status was uncertain all week.
Also sitting out are offensive guard Shawn Andrews and wide receiver Reggie Brown.
The Eagles (2-3) will need Westbrook healthy down the stretch. The team's bye is next week.
"I think the bye week will help him," Head coach Andy Reid said Friday. "I think it will take some of the sting out of that thing. If he were to get hit on it this week, it would slow down the process of healing."
Although not as potent on offense, the team was riding high after a 15-6 defensive showcase brought down the Pittsburgh Steelers.
Since Week 2, the offense has only scored 52 points, or less than 18 points per game.
The Eagles will be looking to stay afloat in the hyper-competitive NFC East as they face a 49ers team that is no longer a guaranteed win. The Niners' defense has improved, but still ranks 18th against the pass and 23rd against the run.
The Eagles are going to have to take advantage of this, even without Westbrook in the lineup. The 49ers defense features a mix of young and veteran players that are going to look to take advantage of Westbrook's absence.
San Francisco strong safety Michael Lewis--a former Eagle, is fourth among all defensive backs with 35 tackles this season. The team is also tied for 4th in the NFL with 7 interceptions, one of which was taken back for a score.
To win, quarterback Donovan McNabb will have to play mistake-free and spread the ball around, something he has made a career out of. Rookie DeSean Jackson is on pace to have a 1,000+ yard season, and the reserve wide receiver corps has been very good.
The Eagles will also be getting extra help. Veteran wideout Kevin Curtis is expected to get his first action of the season Sunday. A sports hernia injury cost him the second half of preseason, as well as the first stretch of regular season games.
"Kevin is working at a high level. He is close." Offensive coordinator Marty Mornhinweg said Thursday. "He is feeling pretty good. He felt pretty good yesterday; he is feeling pretty good today. He is pretty close. He is a day-to-day situation."
The Eagles are also going to need help from their reserve running backs. Filling in for Westbrook, backup Correll Buckhalter has two touchdowns this season.
Sunday's game will be telling for the Philadelphia offense. McNabb called a players-only meeting on Monday which will hopefully translate to better execution for the Eagles.
If not, Iggles fans could be in for a long, frustrating season.