But while the team's starters will be spending most of the evening watching from the sidelines, a number of players will be trying desperately to grab one of the few roster spots still open. Teams must trim from 75 players to 53 by Saturday, so this is the final chance for several to impress coach Mike Singletary, who has final say on the roster.
Keep an eye on these three who could wind up being the 49ers' bubble boys:
Brit Miller, fullback: Miller appeared to have an inside track early in training camp, but he hasn't played the past two games and seems to have drifted into the background. He can contribute on special teams, so it's possible that special teams coordinator Kurt Schottenheimer might lobby for him, but it's also possible Miller could end up on the practice squad.
Will James, cornerback: Injuries could hurt James, who was signed in May but was unable to practice much in training camp because of a high ankle sprain. In a competition between him and rookie Phillips Adams for the last defensive back spot, Adams wins and could secure his spot with another good game returning punts.
Alex Boone, offensive tackle: The 49ers are well-stocked on the offensive line, but Boone's versatility should be enough to win him a place on the roster. He's working on his familiarity with both tackle spots, which improves his value, and given the number of injuries the line has had so far, he might play a role at some point in the season.