Here's a look at some things to watch from the 49ers' perspective:
Kaepernick's last stand: 49ers coach Chip Kelly hasn't tipped his hand on how his quarterback depth chart will look at the end of the preseason other than to confirm that he believes Blaine Gabbert and Colin Kaepernick are his two best options. Gabbert won't play against the Chargers, while Kaepernick is expected to get an extended look. Putting aside Kaepernick's decision to sit during the national anthem, there's a lot that this coaching staff still needs to learn about him from a football perspective. Kaepernick has taken just 13 live-game reps this preseason. Without an offseason program to get reps, his exposure to Kelly and his staff has been limited. That means Kaepernick will likely have to play with and against backups on Thursday night. It seems exceedingly unlikely that a big performance in that situation would be enough for Kaepernick to win the starting job from Gabbert but it could go a long way in at least solidifying his spot on the roster. Let's not overstate the importance of this game for a quarterback who has started a Super Bowl, but this is a meaningful game in Kaepernick's career, at least as far as his time with the 49ers is concerned.
Whither the wide receivers? An already thin receiver corps got more bad news this week when slot receiver Bruce Ellington was placed on injured reserve because of a severe hamstring injury. DeAndre Smelter (hamstring) has made progress in his recovery but it's unclear if he'll play against the Chargers. The team could use Jeremy Kerley at least on a limited basis. Torrey Smith and Quinton Patton are the other two most accomplished wideouts on the roster and it's unlikely the Niners will play them in the preseason finale. So there's plenty of room for young wideouts who want to step up and claim roster spots. Whether it's Smelter, DeAndrew White, Aaron Burbridge, Dres Anderson, Devon Cajuste or Ryan Whalen, the Niners would undoubtedly like to see someone provide a strong closing argument in San Diego.
Making the case for a third QB: Kaepernick will start and play against San Diego, but he'll be backed up by rookie Jeff Driskel and veteran Christian Ponder. Kelly has said there's no set amount of quarterbacks he wants to keep on the roster, but if he wants to keep three, the Niners will need to decide whether to go with youth or experience. Driskel has flashed his potential at times in the preseason but still needs plenty of polish. Ponder had a strong debut but didn't do much last week against Green Bay. Much of this will depend on what the Niners' plans for Kaepernick are. But if Driskel and/or Ponder can put together a good outing against the Chargers, it could convince the Niners to view things a little differently at the game's most important position.
Sorting out the lines: The 49ers haven't been shy about rotating the lines on both sides of the ball. Again, they probably won't play many of their starters, but there's still plenty to figure out in terms of the depth. On the offensive line, Anthony Davis could probably use more work at right guard since he's played in only one game there since he was a college freshman. He might get a longer look and so, too, could guard Joshua Garnett. Likewise, the Niners need to figure out if they want to go with Davis as their swing tackle or go with someone like Colin Kelly, Fahn Cooper or John Theus for depth.
On the defensive line, the Niners have some tough decisions coming with Glenn Dorsey still working his way back from a knee injury and Quinton Dial sitting out because of a knee injury of his own. When it comes to depth up front, San Francisco has options such as Mike Purcell, Tony Jerod-Eddie and Garrison Smith jockeying for position.