49ers vs Colts Odds, Best Bets & SGP For MNF NFL Week 16

Dec 22nd, 2025 8:02 AM EST

San Francisco 49ers quarterback Brock Purdy (13)

Lucas Oil Stadium’s atmosphere often amplifies offensive storylines when the Colts and 49ers meet, and December 22nd presents another road test for Brock Purdy as his passing yards tend to rise in high-leverage away games. Christian McCaffrey’s all-purpose scoring threat and George Kittle’s recent red-zone success against AFC opponents add volatility and upside, creating an intriguing setup for NFL same game parlay picks today.

Below, we break down the 49ers vs Colts Monday Night Football predictions, and our best 49ers vs Colt same game parlay (SGP) — all designed to give bettors an edge for tonight’s NFL action.

Bookies.com reveals the top NFL Odds for this Monday night showdown.

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49ers vs Colts Odds & SGP For MNF NFL Week 16 Betting Predictions

This combination targets complementary strengths: a quarterback with explosive yardage potential pairs well with versatile touchdown options at running back and tight end. Passing props align naturally here due to Purdy's situational risk-reward play style on the move. Both Kittle and McCaffrey have demonstrated their capacity to finish drives regardless of coverage schemes or location.

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49ers vs Colts Same Game Parlay

1. Brock Purdy Over 229.5 - Player Passing Yards

Brock Purdy has shown both peaks and valleys in away performances this season, but frequently surpasses significant passing thresholds under pressure situations. He reacts well against teams that allow yards after catch opportunities—something Indianapolis has struggled limiting at times this year.

Game tempo should benefit his total attempts given San Francisco’s willingness to leverage short passes as run extensions if needed indoors. Weather won’t be a factor inside Lucas Oil Stadium so deep throws are more viable than late-season outdoor venues offer elsewhere.

2. Christian McCaffrey - 240 - Anytime Touchdown Scorer

Christian McCaffrey remains one of football’s most versatile scoring threats when traveling, producing touchdowns via ground attack or aerial routes alike almost every outing away from home turf in this campaign so far he capitalizes quickly once inside the twenty-yard line thanks largely reliable blocking up front plus Kyle Shanahan scheming mismatches weekly defenses haven’t resolved ways contain him yet there is little reason expect dramatic shift during Sunday's action.

3. George Kittle Over 0.5 - Player Touchdowns

George Kittle thrives particularly as an end zone target versus non-divisional foes which aligns nicely considering Indianapolis’ recurring difficulties defending athletic tight ends over last two months his route flexibility lets him exploit soft spots across intermediate zones while also delivering after-catch explosiveness whenever single coverage appears frequent usage near goal line increases odds for a touchdown grab compared typical weeks look for Shanahan dialing up designed plays specifically aimed towards maximizing these matchups.