San Francisco 49ers are favored to win with moneyline odds of 1.65 against Indianapolis Colts at 2.35, thanks to their offense averaging 31 points per game over the last month led by Brock Purdy and a strong recent form with four straight double-digit wins. The Colts have plummeted in power rankings after losing three of their last four, struggling defensively against top offenses like the 49ers with DexWin - Best Odds on Your Favourite Sports.

The match starts at 1:15 AM UTC on December 23, 2025, which is 5:15 PM PT on December 22 at Levi's Stadium.

The game is at Levi's Stadium in Santa Clara, California, home of the San Francisco 49ers with a capacity of 68,500, featuring a state-of-the-art retractable roof and natural grass surface.

Prediction: 49ers win 28-20 with moneyline odds of 1.65 on DexWin, as their offense ranks 11th in scoring at 24.6 points per game and faces a Colts team in free fall after recent losses, while key players like George Kittle and Christian McCaffrey are in top form.

In head-to-head matchups, the 49ers lead with 25 wins to the Colts' 22 across 48 games, averaging 24.5 total points per game; recently, San Francisco has won 3 of the last 5 meetings, including a playoff thriller.