On Monday, December 22, 2025, the San Francisco 49ers will visit the Indianapolis Colts at Lucas Oil Stadium in Indianapolis. This Week 16 game kicks off at 8:15 PM and will be shown on ESPN. The 49ers, with a 10-4 record, aim to continue their strong season against the Colts, who hold an 8-6 record. Check out more about the San Francisco 49ers and Indianapolis Colts before the game.

49ers vs. Colts Betting Prediction

• Money Line Prediction: San Francisco 49ers at -283. The 49ers have a strong road record this season, going 6-2. They are also coming off a win against the Titans, scoring 37 points.
• Over/Under Prediction: Under 46.5. The Colts’ recent games have been low-scoring, with their last two games totaling 34 and 54 points. The 49ers’ defense ranks 8th in opponent offensive yards, which could limit the Colts’ scoring.

Team Trends

• The San Francisco 49ers have a strong road record this season at 6-2-0.
• The Indianapolis Colts have been successful at home with a record of 6-1-0.
• In their recent game, the 49ers defeated the Tennessee Titans 37-24 at home.
• The Colts recently lost to the Seattle Seahawks 18-16 on the road.
• 49ers’ head coach is Kyle Shanahan, while the Colts’ head coach is Shane Steichen.

49ers vs Colts Preview

The San Francisco 49ers are set to visit the Indianapolis Colts in a Week 16 game at Lucas Oil Stadium. The 49ers hold a 10-4 record and are third in the NFC West. They have been strong on the road with a 6-2 record. The Colts are 8-6 and third in the AFC South, looking to end a four-game losing streak.

Key players to watch include Brock Purdy for the 49ers, projected to pass for 267 yards and score nearly two touchdowns. Christian McCaffrey is also expected to make an impact with over 60 rushing yards. For the Colts, Philip Rivers aims to lead the offense with over 200 passing yards. Jonathan Taylor is set to be a major factor with 102 rushing yards projected.

Indianapolis Colts: Key Players and Season Overview

The Indianapolis Colts have a strong season record of 8-6-0. At home, they shine with a 6-1-0 record. The team is under the leadership of head coach Shane Steichen.

Philip Rivers leads the Colts as the starting quarterback. This game, he is projected to have 200.6 passing yards and 1.5 touchdowns. Jonathan Taylor stands out in the running back position, expected to rush for 102.0 yards.

Michael Pittman Jr. is one of the top wide receivers, with a projected 47.9 receiving yards. Tyler Warren serves as a key tight end, contributing in passing plays. On defense, the Colts are ranked 13th in sacks with 36 this season.

San Francisco 49ers: Road Warriors in Action

The San Francisco 49ers are having a strong season with a 10-4-0 record. On the road, they hold a solid 6-2-0 record. Kyle Shanahan is the head coach, guiding the team from the sidelines.

Brock Purdy leads the 49ers as the starting quarterback. He is expected to throw for 267.0 yards and 1.8 touchdowns in this game. Christian McCaffrey is a key player in the running game, projected to rush for 61.2 yards.

George Kittle is a top target in the passing game, with 66.8 receiving yards expected. The 49ers’ defense is ranked 12th in sacks, with 37 this season. Injuries will affect the team, with key players like Nick Bosa and Fred Warner out for the season.

Final Betting Pick

The San Francisco 49ers have been strong on the road this season, with a 6-2 record. Their recent win against the Titans, where they scored 37 points, shows their offensive capabilities. Brock Purdy is expected to have a solid game, with projected stats of 267 passing yards and nearly two touchdowns. The under 46.5 prediction is supported by the Colts’ recent low-scoring games. The 49ers’ defense is ranked 8th in opponent offensive yards, which might limit the Colts’ scoring opportunities. With the Colts having scored only 16 and 19 points in their last two games, the under seems likely.

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All odds are courtesy of Action247 Sportsbook. Good luck!!

* All odds are provided by Action247 Sportsbook and all odds subject to change. **All views expressed are my own. My picks are my own and are not a guarantee, bet at your own risk. Action247 does not warrant the accuracy of completeness of the information, text, graphics, links or other items contained within these post.