The Week 16 NFL schedule culminates with a compelling Monday Night Football matchup as the San Francisco 49ers visit the Indianapolis Colts at Lucas Oil Stadium, kicking off at 8:15 p.m. ET. The 49ers (10–4) are chasing playoff positioning and momentum after a four-game win streak, while the Colts (8–6) are fighting to stay alive following a recent skid. Tonight’s primetime game features star talents like Christian McCaffrey, Jonathan Taylor, George Kittle, Michael Pittman Jr., and veteran quarterback Philip Rivers making an unlikely return under center. Below, we break down the latest betting odds, prop markets, same-game parlay ideas, player props, trends to watch, and our final prediction.
(Note: Betting odds and player prop lines are subject to change as game time approaches.)
Monday Night Football Betting Odds Overview
San Francisco 49ers at Indianapolis Colts (Week 16 MNF)
- Spread: 49ers −5.5 (some books show −6)
- Moneyline: 49ers ~ −260, Colts ~ +210
- Total (O/U): 46.5 points (range on some books 45.5–46.5)
The 49ers are favored on the road, reflecting their overall momentum, deeper roster, and more consistent scoring output. The total sits in the mid-40s range, suggesting a moderately paced game where defenses and running game scripts could matter.
Game Preview & Betting Breakdown
49ers Offense: San Francisco boasts one of the league’s most balanced offenses. Christian McCaffrey leads the charge as a dual-threat back with elite rushing and receiving production. Tight end George Kittle remains a favorite target in critical situations, and emerging receivers like Jauan Jennings add big-play potential. QB Brock Purdy returned from injury and has maintained a steady rhythm, giving McCaffrey and Kittle plenty of high-value opportunities.
Colts Offense: Indianapolis transitioned to veteran Philip Rivers after injuries to Daniel Jones, giving the old-school QB a chance to use his experience and timing with weapons like Michael Pittman Jr. and slot threats such as Josh Downs. Running back Jonathan Taylor is a focal point of the ground game and remains a high-usage player in both run and short-pass situations.
Injury/Status Notes: The Colts are missing key offensive line pieces, including left tackle Bernhard Raimann, placing added pressure on Rivers’ protection.
MNF Popular Player Prop Betting Markets
Player prop markets often present some of the best value on Monday Night Football, especially in high-usage roles and matchup-driven spots. Below are the most discussed prop categories for tonight’s 49ers vs. Colts matchup, along with a betting lean and the reasoning behind each angle.
Brock Purdy (49ers) — Passing Yards
Lean: Over
Purdy continues to operate one of the league’s most efficient passing offenses, supported by elite yards-after-catch weapons. Against a Colts defense that can struggle to contain play-action and intermediate routes, Purdy’s passing volume should remain steady even if San Francisco establishes the run early.
Christian McCaffrey (49ers) — Rushing Yards & Receiving Yards
Lean: Over (combined usage)
McCaffrey’s role is matchup-proof. Indianapolis has allowed production to versatile backs, and San Francisco frequently uses McCaffrey in motion and mismatches against linebackers. His dual-threat usage creates multiple paths to clearing both rushing and receiving thresholds.
George Kittle (49ers) — Receiving Yards & Anytime Touchdown
Lean: Receiving Yards Over / TD Slight Lean
Kittle’s volatility is well known, but primetime games often bring increased target emphasis. The Colts’ defense has shown vulnerability to tight ends in the red zone, and Kittle remains one of Brock Purdy’s preferred options on play-action near the goal line.
Jonathan Taylor (Colts) — Rushing Yards
Lean: Over (volume-based)
With Indianapolis likely aiming to control tempo and keep San Francisco’s offense off the field, Taylor projects for heavy usage. Even against a strong 49ers front, sustained carry volume gives Taylor a solid path to surpassing his rushing yard total.
Jonathan Taylor (Colts) — Receiving Yards
Lean: Under
While Taylor is capable in the passing game, the matchup and projected game script suggest limited designed targets. Indianapolis may prioritize quick throws to wide receivers rather than checking down frequently against San Francisco’s aggressive pass rush.
Michael Pittman Jr. (Colts) — Receiving Yards
Lean: Over
Pittman remains the clear WR1 and target leader in Indianapolis. In potential catch-up scenarios, he should see consistent volume on short and intermediate routes, especially against zone coverage where his size and route-running excel.
Michael Pittman Jr. (Colts) — Anytime Touchdown
Lean: Slight Over
Pittman is a primary red-zone target, particularly on fades and slants. While touchdowns are inherently volatile, his usage near the goal line makes him one of the most logical Colts scoring candidates.
Josh Downs (Colts) — Receiving Yards
Lean: Over
Downs has emerged as a reliable chain-mover out of the slot. His route tree aligns well against San Francisco’s coverage schemes, and his involvement increases in up-tempo or trailing game scripts.
Player Prop Bet Ideas — 49ers vs. Colts (Week 16 MNF)
| Player | Prop Market | Current Odds / Line | Lean | Reasoning |
|---|---|---|---|---|
| Brock Purdy (49ers QB) | Passing Yards — Over/Under 243.5 | O/U 243.5 (−114/−114) | Over | High play volume & passing opportunities vs. Colts’ secondary concessions. |
| Christian McCaffrey (49ers RB) | Rushing Yards — Over/Under 63.5 | O/U 63.5 (−115/−115) | Over | Dual threat with heavy carries in balanced script. |
| Christian McCaffrey (49ers RB) | Receiving Yards — Over/Under 35.5 | O/U 35.5 (−110/−110) | Over | Valuable in check-downs & mixed routes. |
| George Kittle (49ers TE) | Receiving Yards — Over/Under 60.5–68.5 | ~60.5–68.5 (−110 to −115) | Over | Colts have historically struggled vs. TEs, and Kittle often sees high red-zone volume. |
| George Kittle (49ers TE) | Anytime Touchdown Scorer | +115 / +120 (varies) | Lean Yes | Primary red-zone target with wide open roles if WRs are limited. |
| Jonathan Taylor (Colts RB) | Rushing Yards — Over/Under 97.5–98.5 | ~97.5–98.5 (−115) | Over | High usage if Colts control tempo; volume play. |
| Jonathan Taylor (Colts RB) | Receiving Yards — Over/Under 19.5 | O/U 19.5 (−110/−110) | Under | Secondary receiving role, fewer designed targets. |
| Michael Pittman Jr. (Colts WR) | Receiving Yards — Over/Under 62.5 | O/U 62.5 (−110/−110) | Over | Colts’ clear WR1; volume target if passing. |
| Michael Pittman Jr. (Colts WR) | Anytime Touchdown Scorer | +360 / +375 (varies) | Lean Yes | Go-to red-zone receiver slate. |
| Josh Downs (Colts WR) | Receiving Yards — Over/Under 24.5 | O/U 24.5 (−110/−110) | Over | Trusted slot target especially if Colts are trailing. |
📌 Notes on These Lines
- Purdy’s passing line ~243.5 is drawn from pre-game public feeds — this is a primary QB yardage market available widely.
- McCaffrey’s rushing/receiving lines reflect the matchup and usage patterns — especially valuable in balanced scripts.
- Kittle’s receiving line range accounts for slight differences across major sportsbooks and expert markets.
- Taylor’s rushing yard lines are among the highest volume options from multiple projections.
- Pittman and Downs receiving props are consistent across public projections and consensus lines.
Same-Game Parlay Idea (High Risk / Higher Reward)
- 49ers −5.5
- Christian McCaffrey Over 68.5 Rushing Yards
- George Kittle Anytime Touchdown
This SGP stacks San Francisco’s favorites in volume and red-zone targets, creating a combined leg with elevated payout potential if all hit under the primetime script.
Alternate Player Props Table — 49ers @ Colts (Week 16 MNF)
| Player | Alternate Prop | Typical Odds Range | Betting Lean | Why It Makes Sense |
|---|---|---|---|---|
| Brock Purdy (49ers) | 225+ Passing Yards | −160 to −180 | Lean Yes | High floor in efficient offense |
| 275+ Passing Yards | +155 to +175 | Sprinkle | Game script favors continued passing | |
| Christian McCaffrey (49ers) | 80+ Rushing Yards | −135 to −155 | Lean Yes | Workhorse role regardless of score |
| 100+ Scrimmage Yards | −160 to −190 | Strong Lean Yes | Dual-threat usage nearly matchup-proof | |
| Anytime TD | −135 to −155 | Strong Lean Yes | Primary red-zone option | |
| George Kittle (49ers) | 50+ Receiving Yards | −135 to −155 | Lean Yes | Colts vulnerable to tight ends |
| Anytime TD | +110 to +130 | Lean Yes | Play-action favorite near the goal line | |
| Jonathan Taylor (Colts) | 80+ Rushing Yards | −120 to −140 | Lean Yes | Colts likely commit to run game |
| 100+ Rushing Yards | +135 to +155 | Moderate Risk | Needs positive game flow | |
| Michael Pittman Jr. (Colts) | 60+ Receiving Yards | −125 to −145 | Lean Yes | Consistent target volume |
| 80+ Receiving Yards | +145 to +165 | Upside Play | Game script could boost attempts | |
| Anytime TD | +350 to +400 | Sprinkle | Colts’ top red-zone WR | |
| Josh Downs (Colts) | 40+ Receiving Yards | +120 to +140 | Lean Yes | Slot mismatch if Colts trail |
(Alternate prop lines and odds may vary by sportsbook and are subject to change leading up to kickoff.)
Same-Game Parlay (Alt Props Only) — 49ers @ Colts (Week 16 MNF)
This same-game parlay combines high-floor alternate props for Monday Night Football, focusing on yardage volume rather than volatile touchdown markets.
Parlay Legs
- Christian McCaffrey — 100+ Scrimmage Yards
McCaffrey’s dual-threat role makes this one of the safest alt-yardage thresholds on the board. - Brock Purdy — 225+ Passing Yards
San Francisco’s play-action offense and balanced attack create a high floor for Purdy’s passing volume. - George Kittle — 50+ Receiving Yards
Kittle’s involvement spikes in primetime and against defenses that struggle covering tight ends. - Jonathan Taylor — 80+ Rushing Yards
Indianapolis is expected to lean on the run to manage game flow, giving Taylor a clear path to volume.
Monday Night Football Week 16 Betting Angles & Trends to Watch
- 49ers Spread Performance: San Francisco has performed well ATS in recent games, indicating they may cover road favorites.
- Under/Over Trend: Totals for both teams’ recent games suggest lean toward moderate scoring, making the mid-40s O/U relevant.
- Colts Run Game: Indianapolis has leaned on Taylor and short completions under Rivers, which can slow the pace and keep totals in check.
Final MNF Betting Prediction
Expect a battle between a balanced 49ers offense and a Colts squad relying on experience and short passing. Our lean: 49ers −5.5 to cover, with the total trending Under ~46.5 due to clock control and balanced rushing involvement. McCaffrey and Kittle should remain focal points for volume, while Taylor’s role keeps the Colts competitive and helps control tempo.
All odds and predictions are for informational and entertainment purposes only. This content does not constitute betting advice from BetHouse.com