NFL Predictions Week 16: Best Bets & Odds for Monday Night Football
Last Updated: December 22, 2025 9:33 PM EST • 1 minute read X Social Google News Link
With just one game left this week, our NFL predictions for Week 16 focus on the Monday Night Football clash tonight between the San Francisco 49ers (10-4) and Indianapolis Colts (8-6) at Lucas Oil Stadium in Indianapolis. We've gathered all of our best ATS picks, player prop bets, and touchdown scorer predictions tonight.
🏈 NFL predictions for Monday Night Football: Week 16
See the latest NFL odds and the rest of our NFL picks for every game this season.
💰 NFL odds and expert picks: Monday Night Football
See the latest Monday Night Football odds and our best TNF predictions.
49ers vs. Colts odds & prediction
- Date: Monday, Dec. 22
- Kickoff: 8:15 p.m. ET
- Location: Lucas Oil Stadium (Indianapolis)
- TV: ESPN
⬆️ Over 46.5 (-102)
Since Week 11, when quarterback Brock Purdy returned from injury, the 49ers rank fourth in points per game (31.0), second in Total QBR, first in third-down rate, and sixth in Offensive Efficiency.
- via Mike Spector's 49ers vs. Colts prediction
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C Jackson Cowart X social