The San Francisco 49ers have a decision to make on Brandon Aiyuk, with Week 6 serving as a key checkpoint. His status remains procedural, not scheduled, and the next transaction will signal how close he is to returning.
What Happened To Brandon Aiyuk? Latest Injury Update
Aiyuk tore the ACL and MCL in his right knee on October 20, 2024, against the Kansas City Chiefs, ending a seven‑game season in which he posted 25 receptions for 374 yards. He opened 2025 on the active Physically Unable to Perform (PUP) list in mid‑July and moved to reserve PUP on August 26.
Reserve PUP rules require a player to miss at least the first four games. That threshold passed two weeks ago, which means Aiyuk is eligible to return, but only after the team files a “designated to return” transaction that opens a 21‑day practice window.
As of the latest Week 6 reporting, San Francisco has not made that designation and Aiyuk does not appear on the participation report, which is consistent with his current roster status.
GM John Lynch spoke a bit on WR Brandon Aiyuk today – “he’s working really hard, he’s coming along, he’s making strides…” Lynch last week said Aiyuk wasn’t have any big setbacks but just wasn’t at the point where they thought he would be so hopefully Aiyuk is close to coming pic.twitter.com/3lVffnglsX
— 49er_Edits (@49er_edits) October 9, 2025
Internally, the timeline has been framed as a range rather than a fixed date. Head coach Kyle Shanahan previously said he “starts thinking about” a comeback in the Week 6 neighborhood, while also noting the real timetable can slide earlier or later based on rehabilitation milestones and medical clearance.
General manager John Lynch reiterated this week that the club will move only when benchmarks are met, not by the calendar. Procedurally, once Aiyuk is designated to return, he can practice immediately for up to 21 days, and activation can occur any time in that window. If the window expires without activation, the team must keep him on PUP until he is again eligible.
Will Brandon Aiyuk Play In Week 6?
A Week 6 appearance is not expected. Aiyuk has not been designated to return, has not practiced, and is therefore ineligible to play this weekend. Earlier comments left open the possibility of a mid‑October window, but the team’s actions this week indicate his ramp remains ongoing and will continue to be driven by medical clearance rather than the schedule.
When San Francisco opens his practice window, the sequence is expected to be streamlined, with controlled practice work, medical evaluation of post-practice response, and activation at any point during the 21-day period once he is ready.
Until then, the 49ers will continue to spread targets among available receivers and tight ends while monitoring daily updates from the training staff and filing any changes on the transaction wire and practice reports.