The Colts suffered only the second losing season of Peyton Manning's career. After opening with dominant wins over the Jets and Buffalo, the Colts were crushed twice in three games by the Patriots to go with a loss to Oakland. Two more wins followed but the season fell apart with losses in seven of the season's final nine games; a 40–21 rout by the San Francisco 49ers on national television set off an infamous postgame press conference rant by coach Jim Mora in which he harped on four Manning interceptions, repeatedly noting one was returned (by the Niners' Zack Bronson) for a touchdown and the others set up San Francisco scores, and a fumble; he angrily scoffed at a reporter's question about the Colts' playoff chances when he barked, "Ah, p-p-p-Playoffs?!? Don't talk about...playoffs? You kidding me? Playoffs? I just hope we can win a game!" Mora was fired after the season.
Manning threw 23 interceptions during the season, the highest number of his career following his rookie season. He was sacked a career-high 29 times.