San Francisco and Denver have faced off 13 times in the regular season, plus in Super Bowl XXIV, when the 49ers won, 55-10, in New Orleans.
Denver -- Week 3 of the NFL preseason is widely referred to as the dress rehearsal for the regular season.
The San Francisco 49ers have been in Denver since Tuesday, and after two joint practices with the Broncos, the two teams are set to square off on Saturday night from Sports Authority Field at Mile High.
The game will mark the 37th preseason meeting between the 49ers and Broncos and continue a streak of playing each other every year since 2012. Each team is implementing new systems on both sides of the football, which makes this contest a particularly interesting one to watch.
Colin Kaepernick and the 49ers first-team offense have only seen three series of playing time through two preseason games, but should be in line for extended work against the Broncos. Kaepernick and Torrey Smith have been inches away from a touchdown in each of the first two preseason games. This could be the game Smith records his first reception in red and gold.
In addition to the starters likely playing longer into the game, 49ers fans may catch their first glimpses of running backs Reggie Bush and Kendall Hunter. For Hunter, it will be a return to football after missing all of 2014 due to an ACL. As for Bush, any snaps the veteran ball carrier sees will be his first in a 49ers uniform.
Here are five more things to watch as the 49ers go for their second win in a row. 1. 49ers cornerbacks vs. Peyton Manning & Co.
Broncos head coach Gary Kubiak told the media on Wednesday that he plans on having his first-team offense on the field for at least the first half. There will likely be a rep count on Manning's snaps, which could force him to exit before halftime. But the quarterback will still provide an excellent challenge for the 49ers cornerbacks.
The team's top corner, Tramaine Brock, left Thursday's practice with a muscle strain in his leg. His status for Saturday is unknown at this point. If Brock does miss the game, look for Kenneth Acker, Dontae Johnson, Keith Reaser and Shareece Wright to continue their strong play and carry the responsibility of covering Damaryius Thomas and the rest of a talented group of Broncos receivers.
2. Round 2 for Bo
Head coach Jim Tomsula had NaVorro Bowman's snap limit at five plays last week against the Dallas Cowboys. The 49ers star linebacker only needed three, recording a tackle on each play in his return to game action. We don't know what Bowman will be held to on Saturday, but when No. 53 is on the field, he is always a player to watch.
3. Staley vs. Von Miller and DeMarcus Ware
A premier left tackle vs. two premier pass rushers. It will be a fantastic tune-up for Joe Staley, and the rest of the 49ers offensive line for that matter, to be able to go up against one of the NFL's best tandems at getting to the quarterback.
Staley said he knows what he's getting from the two Broncos defenders after the joint practices Wednesday and Thursday.
"His speed and his power," said Staley, identifying what Miller's biggest strengths are. "His get-off and the power he plays with are unmatched in the NFL. It's been great work for us."
Staley has been a stalwart for the 49ers at left tackle since 2007 and will continue to anchor the offensive line in 2015.
4. Patton, Ellington, White & the battle to be the No. 3 WR
The battle for the team's third receiver job behind Anquan Boldin and Smith remains one of the most intriguing competitions on the 49ers roster.
Those reserve receivers will all get plenty of playing time against the Broncos as long as their health permits. Quinton Patton blocked a punt and returned it for a touchdown against the Cowboys. Bruce Ellington this week returned to the field after dealing with a muscle strain. DeAndrew White will look to transfer his knack for making big plays in practice into a game situation.
Those are the top three candidates for the job, and maybe after the Broncos game there will be a clearer picture of how they stack up against each other.
5. The "Hayne Plane"
There's no denying this storyline. Both Tomsula and Jarryd Hayne himself have tempered the media attention of the running back's play thus far, but eyes will still be zeroed in on No. 38 Saturday night.
Hayne's 117 rushing yards is the second most in the NFL so far this preseason and his yards per carry average of nine yards is the most of any running back with at least five rushing attempts. Hayne also has five punt returns for 108 yards (21.6-yard avg.) and one kick return for 33 yards.
As Tomsula said after the 49ers win against the Cowboys, Hayne is certainly making a case for himself to earn a spot on the 53-man roster. However, with Pierre Garçon expected to see more playing time as well as Bush and Hunter returning to the lineup, Hayne will be a part of a more crowded backfield on Saturday.