On Friday, the 49ers announced that the veteran wide receiver has been placed on injured reserve after missing Monday night's win over the Atlanta Falcons with a setback to his surgically repaired left knee.
Coach Jim Harbaugh told reporters Friday that Manningham will "consult with doctors and do what's in the best interest of his career" after departing Thursday's practice with lingering knee discomfort.
The veteran wideout played in six games after spending the first half of the season on the physically unable to perform list to rehab the torn ACL he suffered last December. With just nine catches for 85 yards on the year, Manningham's absence will push rookie Quinton Patton into the lineup as the third wideout behind Michael Crabtree and Anquan Boldin.
Set to become a free agent in March, it's likely Manningham's days in red and gold are all but over.