The San Francisco 49ers started out the season 1-0 with an important divisional win over the Seattle Seahawks. However, the first game of the season was incredibly costly, with Brock Purdy and George Kittle both suffering notable injuries. Even with very winnable games ahead, there is now a question mark of what the 49ers' offense is going to look like when dealing with so many injuries across the board.
A big piece of this is understanding that we are getting at least two weeks of backup quarterback Mac Jones, who has had an uneven history as a starter. The hope here is that playing in the most talented offense of his career is able to unlock Jones and push the quarterback to be the version of himself we watched in his rookie season. With this in mind, let's take a look at and predict the results of each of San Francisco's next four games.
Week 2 - San Francisco 49ers @ New Orleans Saints, Sept. 12th
This might be the only team in the league the 49ers could start against in the league right now and have a decided quarterback advantage. Spencer Rattler is the current New Orleans starter on an offense that was underwhelming in Week 1 vs. Arizona. So much of the Saints' roster is in need of a rebuild, and both sides of the ball reflect this. Apart from the quarterbacks, the 49ers have such a decided advantage in the trenches.
San Francisco is going to be able to push around the Saints on both sides of the ball, making life far easier on Jones. If Christian McCaffrey is going to have a breakout game in the next weeks of the season, there is no better setup than this matchup.
Regardless, the 49ers aren't going to drop this game even without the benefit of their franchise quarterback. Look for the 49ers to grind out the clock and work to shorten a game in which Rattler is destined to consistently miss throws and help take the pressure off Jones by making more than his fair share of mistakes.
Final Score: 49ers 24 - Saints 13
Week 3 - Arizona Cardinals vs. San Francisco 49ers, Sept. 21st
This is going to be the first true test for the 49ers without the benefit of a franchise quarterback. Doubting this coaching staff is unwise, however, there is no denying that Arizona's offense appears to have a better roster with its current healthy weapons. If both rosters were fully healthy, there is zero question that the 49ers are the better unit.
If you're going to make an argument for the 49ers to win this game, it is based on a superior defense creating turnovers from Kyler Murray and making life easier on Mac Jones. If Robert Saleh's defense isn't at its absolute best in Week 3, there is a very real chance the game slips out of hand. However, it is only fair to point out not only the far more talented defense for the 49ers, but clearly superior coaching.
The deciding factor in this game is going to be how well the 49ers can hide Jones while making life hard on Murray. There is zero legitimate reason to doubt Kyle Shanahan's staff is going to get the job done in what will be a nail-biter.
49ers 19 - Cardinal 17
Week 4 - Jacksonville Jaguars vs. San Francisco 49ers, Sept. 28th
This is the first game that is truly difficult to predict, as we don't yet know whether or not Brock Purdy will be back in the lineup. Purdy's current injury will have the QB out of the lineup for 2-5 weeks, making this the first possible return. Making it extremely difficult to know what this game will look like. However, considering Purdy's toughness and limited injury, let's work under the assumption that the quarterback is going to be able to return to the lineup.
It will be a matchup against Trevor Lawrence and a Jaguars franchise that continually cannot get out of its own way. Travis Hunter and Brian Thomas Jr. are the only even slightly concerning factors in Jacksonville's lineup. San Francisco is the more talented team in the trenches and that is going to become very obvious early in the game.
As long as Purdy is able to return to the lineup look for the 49ers to jump out to an early lead and run out the clock.
49ers 27 - Jaguars 23
Week 5 - San Francisco 49ers @ Los Angeles Rams, Oct. 2nd
This is going to be the first real test for the 49ers of the 2025 season, with the Rams having an incredibly talented defensive front and the more accomplished quarterback in Matthew Stafford. These games are always incredibly entertaining with the two head coaches who are arguably the most talented offensive minds in the league.
Regardless, this season has a series split written all over it between the division's best two teams. Making it very plausible that each team is going to defend its home turf, giving a closely fought game to the Rams.
Two important notes here, however, in that this is working under the assumption Purdy will be back and Stafford remains in the starting lineup. Obviously, either of these factors changing gives a completely different result. With this in mind, if the starting lineups remain intact, this is going to be the start of a series split with the Rams stealing the first game.