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Indianapolis Colts vs San Francisco 49ers Betting Preview
San Francisco enters Monday night looking to extend its win streak to five games and remain within striking distance of the NFC West lead. The 49ers sit at 10-4, trailing Seattle and Los Angeles, and can clinch a playoff berth with a road victory. Brock Purdy has returned to form after a toe injury, while Christian McCaffrey continues to anchor the offense through balanced usage and scoring efficiency.
Indianapolis enters 8-6 and remains firmly in the AFC playoff chase despite last week’s 18-16 loss to Seattle. The Colts sit one game behind Houston and two behind Jacksonville with divisional matchups looming over the final two weeks. Philip Rivers, now 44, makes his second straight start, and Jonathan Taylor continues to lead the league in rushing yards and touchdowns.
Both teams have division-title pathways, and both rely heavily on elite running backs and structured defensive play. San Francisco’s offensive rhythm has returned with Purdy and McCaffrey healthy, while Indianapolis looks to regain its early-season form after four straight losses.
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Line Movement and Odds
San Francisco opened -4.5 and has climbed to -5.5 as early action backed their balanced offense and late-season momentum. Indianapolis is +5.5 with interest tied to Taylor’s workload and home-field stability.
The total opened 44.5 and has remained unchanged. Both teams lean on the run, creating a projected slower tempo despite explosive-play talent.
Track updated movement on the NFL odds board.
Matchup Breakdown
Indianapolis leans heavily on Taylor and early-down efficiency. Rivers brings veteran decision-making and can stabilize the passing game through rhythm-based concepts, but explosive plays remain limited. Defensively, the Colts rely on front-seven discipline and interior pressure, although recent breakdowns against the run have shifted their identity. Their pathway requires controlling possession, minimizing negative plays and forcing Purdy into tighter windows.
The 49ers operate through spacing, timing and matchups. Purdy distributes efficiently when protected, and McCaffrey’s versatility creates leverage across formations. San Francisco’s front seven dictates tempo and creates favorable field position. Their challenge lies in handling Taylor’s workload and maintaining coverage integrity against Rivers’ anticipatory throws.
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Key Information
Sport: NFL
Matchup: San Francisco 49ers vs Indianapolis Colts
Venue: Lucas Oil Stadium, Indianapolis, IN
Date: Monday, December 8, 2025
Game Time: 8:15 PM ET
Broadcast: ESPN
Betting Odds (Projected Market Consensus)
49ers Moneyline: -225
Colts Moneyline: +185
49ers Spread: -5.5 (-110)
Colts Spread: +5.5 (-110)
Total: 44.5 (O/U -110)
The 49ers Can Win If…
San Francisco sustains rhythm through McCaffrey and avoids turnover volatility. Purdy has regained timing and movement patterns since returning from injury, and his short-area efficiency allows the 49ers to stay ahead of schedule. Defensively, maintaining gap integrity against Taylor and generating third-and-long situations will force Rivers into tighter-window throws. Field position and disciplined coverage are central to their advantage.
49ers Injury Report (Projected)
Ricky Pearsall, knee/ankle, questionable
Spencer Burford, knee/ankle, questionable
Jordan Elliott, knee, questionable
Nick Martin, concussion, out
Full depth chart updates available on the 49ers team page.
The Colts Can Win If…
Indianapolis redistributes early-down touches and stabilizes protection for Rivers. Taylor’s usage needs efficiency, not volume, to keep the offense balanced. Rivers can exploit soft zones and leverage intermediate timing routes if the Colts stay out of predictable passing situations. Defensively, Indianapolis must win at the line of scrimmage and limit McCaffrey’s receiving production, which shapes San Francisco’s third-down conversions. Red-zone execution remains the deciding factor.
Colts Injury Report (Projected)
Sauce Gardner, calf, questionable
Anthony Gould, foot, questionable
Bernhard Raimann, elbow, questionable
Latest Betting Trends (Modeled)
49ers SU last 5 games: 5-0
49ers ATS last 5 games: 4-1
Colts SU last 4 games: 0-4
Colts ATS last 4 games: 1-3
49ers O/U last 6 games: 4-2
Colts O/U home games: 3-1
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Best Bets and Prediction
San Francisco holds structural advantages across both sides of the ball, and their recent form suggests continuity in execution. Indianapolis must create game-flow disruption through turnovers and long drives, but their late-season inconsistency limits their scoring ceiling.
Projected Score: 49ers 27, Colts 20
Best Bet: 49ers -5.5
Secondary Lean: Over 44.5
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