San Francisco (10-4) at Indianapolis (8-6)
When: Monday, December 22nd 2025
Where: Lucas Oil Stadium,
Indianapolis, IN
Time: 8:15 ET | TV: ESPN
Opening Odds: San Francisco -5.5/46
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49ers vs Colts Recent Meetings
Prediction
This is a big game for both teams. San Francisco needs just a win to clinch a playoff berth, while the Colts desperately need a victory and some help over the remaining two weeks. I like the Colts at home in this one getting almost a touchdown. Philip Rivers wasn’t terrible last week on the road against a very good Seattle team. He now has a full week of practice with his new team and should fare even better this week. The 49ers are dead last in sacks, so Rivers may not have to run around as much. The Colts can control the line of scrimmage. They lead the NFL in rushing touchdowns, while ranking second by allowing just 3.7 yards per rush. Indy has also won five straight meetings against San Francisco, including nine of 12 at home. Give me the points.
Pick: Colts +5.5
