Mac Jones is set to start for San Francisco after a knee scare, with Adrian Martinez not elevated. Eli Apple was added from the practice squad for Sundays game against Jacksonville, signaling confidence in the rest of the depth chart. Ricky Pearsall and Jauan Jennings are questionable but likely to play, keeping Bourne, Robinson, Valdes-Scantling and Skyy Moore as viable targets if one sits. Colby is questionable; Moss or Zakelj could step in. Brandon Aiyuk’s absence remains the defining storyline for the offense.

If Pearsall and Jennings sit, the 49ers would lean on a shallow WR corps; if one plays, expect a broader distribution with the expected nod to Bourne and the Chiefs pairing of Robinson, Valdes-Scantling and Moore. The 49ers will list inactives 90 minutes before kickoff at Levi’s Stadium.

San Francisco’s interior line depth is being tested early. Ben Bartch’s high ankle sprain leaves the guard position thinner than anticipated, with Connor Colby questionable for Week 3. If Colby sits, Drew Moss and Nick Zakelj are poised to step in as potential starters, while Arizona presents a stiff Week 3 test for the reshuffled line. Fantasy managers should monitor Colby’s availability and Moss’s activation to gauge inside run game and protection against the Cardinals.

Connor Colby stepped in when Ben Bartch sustained a high ankle sprain, and his Week 2 showing suggested he can handle left guard duties. He posted zero pressures on 38 pass-blocking snaps and earned a 73.1 pass-blocking grade, signaling solid early integration into the 49ers’ interior. Bartch’s injury opens a door for Colby to lock onto the job, at least temporarily, as San Francisco weighs its cost-controlled rookie options.

Bartch’s modest one-year deal and the team’s pursuit of affordable, draft-driven depth make Colby’s rise particularly significant. With Dominick Puni in the mix and Nick Zakelj pushed down the depth chart, Colby could form a compelling guard duo with Puni, enabling a longer window of contention for a squad chasing another title run while contending with OL fragility.

Ben Bartch’s high-ankle sprain sidelines the 49ers’ left guard, forcing the team to lean on a rookie and reshuffle the interior line as Week 2’s run game showed promise behind the left guard. Colby stepped up in Bartch’s absence and impressed, hinting he could secure the starting job if Bartch goes IR, with Moss or Zakelj as immediate practice-squad options.

Spencer Burford’s knee injury adds another layer of uncertainty, while Jauan Jennings’ ankle, Kyle Juszczyk’s concussion protocol, and Siran Neal’s concussion evaluation keep SF’s skill positions and blocking schemes in flux. Robert Beal joining the practice squad stabilizes depth, and Colby’s early success could free up the offense to lean on the run more efficiently as the season progresses.

Overall, SF is navigating an injuried-heavy week with a rookie stepping up, potential IR moves looming, and a handful of players in concussion protocol, all while aiming to maintain offensive pace behind a revamped front five and a broader receiving corps.

Isaiah Prince left San Francisco's preseason finale with a left‑leg injury, casting doubt on the 49ers' early depth at offensive tackle as rosters tighten. With Prince potentially sidelined, Austen Pleasants, Spencer Burford, and Nick Zakelj figure to absorb extra work and shape the Week 1 line, which in turn could impact run blocks and pass protection for the backfield.

Burford’s versatility, Zakelj’s length, and Pleasants’ depth role become fantasy-relevant if Prince misses time, since any extended absence could shift linemen roles and influence SF’s early-season efficiency in both the run game and the pass game. Managers should watch Prince’s timeline and any IR chatter as cuts loom.