2020 record: 6-10
Coach: Kyle Shanahan (5th year with 49ers, 29-35)
2021 Additions: C Alex Mack, OLB Samson Ebukam, DE Zach Kerr, WR Mohammed Sanu, S Tavon Wilson, DT Maurice Hurst, DE Arden Key, RB Wayne Gallman, QB Nate Sudfeld, OLB Nate Gerry, WR Bennie Fowler
2021 losses: WR Kendrick Bourne, DE Kerry Hyder, QB C.J. Beathard, CB Akhello Witherspoon, DE Solomon Thomas, WR Marquise Goodwin, RB Tevin Coleman, RB Jerrick McKinnon, LB Joe Walker, WR Trent Taylor
2021 draft class: QB Trey Lance, OL Aaron Banks, RB Trey Sermon, CB Ambry Thomas, OL Jaylon Moore, CB Deommodore Lenoir, S Talanoa Hufanga, RB Elijah Mitchell
At A Glance: The big move for the 49ers was trading up from No. 12 to No. 3 and selecting North Dakota State's Trey Lance, who GM John Lynch and coach Kyle Shanahan view as the team's quarterback of the future. But how soon will Lance — who only played one game in 2020 amid the COVID-19 pandemic — take over for incumbent starter Jimmy Garoppolo? That'll be a dominant storyline to follow, especially since San Francisco has its bye week before playing the Colts in Week 7.
Star Power: Nick Bosa suffered a season ending knee injury in Week 2 of the 2020 season but as long as he's healthy in 2021, he'll be expected to be one of the most impactful pass rushers in the league. The former No. 2 overall pick was named the AP Defensive Rookie of the Year in 2019 after he totaled nine sacks, 16 TFLs and 25 quarterback hits.
All-time series: 26-18
Last matchup: Week 5, 2017 at Lucas Oil Stadium - Colts 26, 49ers 23 (OT)
The 49ers lost their first nine games of the 2017 season, with this one among the most painful. A Brian Hoyer touchdown to George Kittle tied the game at 23 with 20 seconds remaining, but Adam Vinatieri ripped a game-winning 51-yard field goal in overtime to deal San Francisco its fifth of those one losses.
Upcoming matchup: Week 7, October 24 at Levi's Stadium