| 2026Week 9 · Las Vegas | Gracen HaltonDefensive line | Fractured and dislocated ankle The 49ers placed Halton on injured reserve on November 10 after he had started six games. | 49ers ↗49ers follow-up ↗ |
| 2026Week 6 · Washington | Mike EvansWide receiver | Achilles tendinitis Evans left the Washington game before halftime. By November 11, the receiver had missed two games. | Reuters ↗SF Chronicle ↗ |
| 2026Week 2 · Miami | Demarcus RobinsonWide receiver | High ankle sprain Robinson missed five games. San Francisco activated him from injured reserve ahead of the Raiders game. | NBC Sports ↗ |
| 2025Wild Card · Philadelphia | George KittleTight end | Torn Achilles Kittle’s first catch of the game was his last of the postseason. He left in the second quarter of the win in Philadelphia. | NFL ↗ |
| 2025Week 9 · N.Y. Giants | Mykel WilliamsDefensive line | Torn ACL and meniscus injury The first-round pick’s rookie season ended in the win over the Giants. | 49ers ↗ |
| 2025Week 6 · Tampa Bay | Fred WarnerLinebacker | Fractured and dislocated ankle The 49ers lost their defensive captain for the rest of the regular season. | 49ers ↗ |
| 2025Week 3 · Arizona | Nick BosaDefensive end | Torn right ACL Bosa left in the first quarter against Arizona. The injury ended his season. | 49ers ↗ |
| 2024Week 13 · Buffalo | Christian McCaffreyRunning back | Knee ligament injury (PCL) Four games into his return from Achilles trouble, McCaffrey hurt his knee in Buffalo and missed the rest of the season. | 49ers ↗49ers follow-up ↗ |
| 2024Week 13 · Buffalo | Jordan MasonRunning back | High ankle sprain Mason had filled in for McCaffrey earlier in the year. The Buffalo game sent both backs to injured reserve. | 49ers ↗ |
| 2024Week 7 · Kansas City | Brandon AiyukWide receiver | Torn ACL and MCL Aiyuk hurt his knee on a catch just before halftime. He missed the remainder of the season. | 49ers ↗ |
| 2023Super Bowl LVIII · Kansas City | Dre GreenlawLinebacker | Torn Achilles Greenlaw went down running onto the field after a punt. He missed the rest of the Super Bowl, including overtime. | NFL ↗ |
| 2023Week 11 · Tampa Bay | Talanoa HufangaSafety | Torn ACL The starting safety missed the rest of the season, including the 49ers’ run to the Super Bowl. | 49ers ↗ |
| 2022NFC Championship · Philadelphia | Brock PurdyQuarterback | Torn elbow ligament (UCL) Hurt on the opening drive, Purdy returned after Johnson went down but could barely throw. His right elbow needed surgery. | 49ers ↗49ers follow-up ↗ |
| 2022NFC Championship · Philadelphia | Josh JohnsonQuarterback | Concussion Johnson replaced Purdy and left in the third quarter, forcing the injured starter back into the game. | 49ers ↗49ers follow-up ↗ |
| 2022Week 13 · Miami | Jimmy GaroppoloQuarterback | Fractured foot Garoppolo left against Miami. Rookie Brock Purdy took over the offense. | 49ers ↗ |
| 2022Week 2 · Seattle | Trey LanceQuarterback | Fractured right ankle A broken fibula and ligament damage required surgery. Jimmy Garoppolo took over in the home opener. | 49ers ↗NFL ↗ |
| 2021Week 1 · Detroit | Raheem MostertRunning back | Knee cartilage injury Mostert’s season lasted two carries. He opted for surgery after the opener. | NFL ↗ |
| 2021Week 1 · Detroit | Jason VerrettCornerback | Torn ACL The starting cornerback lost the rest of his season in the opening win over Detroit. | 49ers ↗ |
| 2020Week 2 · N.Y. Jets | Nick BosaDefensive end | Torn ACL His second NFL season ended in the first quarter against the Jets. | 49ers ↗ |
| 2020Week 2 · N.Y. Jets | Solomon ThomasDefensive line | Torn ACL Thomas went down in the same quarter as Bosa. Both defensive linemen missed the rest of the season. | 49ers ↗ |
| 2019Week 14 · New Orleans | Weston RichburgCenter | Torn patellar tendon The 49ers won in New Orleans but lost their starting center for the rest of the season. | 49ers ↗ |
| 2019Week 9 · Arizona | Kwon AlexanderLinebacker | Torn pectoral muscle Alexander went on injured reserve after the Arizona game and missed the rest of the regular season. | 49ers ↗ |
| 2018Week 3 · Kansas City | Jimmy GaroppoloQuarterback | Torn left ACL A fourth-quarter scramble ended Garoppolo’s season three games into his first full year as the starter. | NFL ↗ |
| 2018Preseason · Practice | Jerick McKinnonRunning back | Torn ACL The new signing hurt his knee in practice before the opener and missed his first season with San Francisco. | NFL ↗ |
| 2017Week 8 · Philadelphia | Pierre GarçonWide receiver | Neck fracture (C5) Garçon went on injured reserve while leading San Francisco with 40 catches for 500 yards. | 49ers ↗NFL ↗ |
| 2016Week 4 · Dallas | NaVorro BowmanLinebacker | Torn left Achilles San Francisco lost its middle linebacker for the remaining twelve games. | NFL ↗49ers ↗ |
| 2015Last appearance · Week 7 · Seattle | Carlos HydeRunning back | Foot stress fracture After the Seattle game, Hyde never returned to the lineup that season. He finished the year on injured reserve. | NFL ↗ |
| 2014Week 7 · Denver | Daniel KilgoreCenter | Broken leg Seven games into his first season as the starting center, Kilgore broke his leg. His recovery stretched into 2015. | 49ers ↗ |
| 2014Week 6 · St. Louis | Patrick WillisLinebacker | Left big toe injury Willis aggravated a long-running injury against the Rams. Surgery ended his season. | 49ers ↗ |
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