Week 16 of the 2025 NFL season concludes with Monday Night Football between the 49ers and Colts. The 2nd start of Philip Rivers’ comeback puts him in primetime, so all eyes – including those of the home crowd at Lucas Oil Stadium in Indianapolis – will be on the 44-year-old. Having slumped to an 8-6 record, the Colts need a win in the worst way. It’s a big game for San Francisco, too, as it tries to stay in contention for the NFC West title after wrapping up a playoff berth yesterday. With plenty on the line, let’s break down our 49ers vs Colts Same Game Parlay picks, which gets underway at 8:15 pm ET on ESPN. We nailed +650 and +407 winners in BOTH Saturday games, so let’s add another here! You can also get our expert NFL picks for EVERY game this season.
49ers -5.5 (-108)
George Kittle to score a touchdown (+120)
George Kittle to record 80+ receiving yards (+156)
49ers vs Colts parlay odds: +600
Part of the value in a Same Game Parlay, of course, is that all of its components can be correlated if you so choose. That is the entire plan here, as San Francisco tight end George Kittle having a huge day at the office would obviously work well with the 49ers winning and covering. Let’s break down each of the 3 legs.
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San Francisco 49ers -5.5 over Indianapolis Colts (-108)
In Rivers’ first start of his unexpected 2025 comeback, Indianapolis actually managed to stay competitive at Seattle in an 18-16 loss. However, let’s pump the brakes on talk of Rivers being some kind of heroic grandfather. Yes, he accounted himself well all things considered – but he averaged just 4.4 yards per pass attempt and, for the most part, did little other than hand the ball off to Jonathan Taylor. Rivers now faces another stellar defense in the 49ers, who are giving up just 106.1 rushing yards per contest. You know that unit is going to stack the box and force Rivers rather than Taylor to beat it.
On the other side of the ball, San Francisco QB Brock Purdy has been turnover-free in 3 of 4 games since returning from injury. The Niners have won 4 games in a row, all by at least 11 points. Their last 6 victories have all been by double-digit margins.
Check out Chris Farley’s 49ers vs Colts predictions for MNF — he’s hit 14 of his last 18 picks!
George Kittle to score a touchdown (+120)
With Brandon Aiyuk and Ricky Pearsall sidelined by injuries, the 49ers’ wide receiver room is among the worst in the NFL. Kittle will likely have to do most of the heavy lifting – again – along with Christian McCaffrey in the pass-catching department. That is nothing new for the 32-year-old, who has scored 6 touchdowns in just 9 games this season. He has found the end zone 4 times in the last 5 contests, including once in last weekend’s victory over Tennessee. It’s also worth noting that the Colts have allowed the 11th-most fantasy points to tight ends in 2025.
Now check out our expert’s 49ers vs Colts touchdown scorer best bets, including a prediction at +280 odds!
George Kittle to record 80+ receiving yards (+156)
Kittle has made 45 catches for 484 yards through 9 games this year. He has recorded at least 67 receiving yards in 5 consecutive contests heading into Monday’s matchup, so asking him to reach the 80 mark does not seem overly exorbitant. Even though Indy’s defense is solid, this should be a relatively favorable matchup for Kittle. The Colts are 2nd-last in the NFL against the pass, surrendering 247.6 yards per game. By comparison, they are 6th against the run and 2nd in yards per rushing attempt allowed.
Don’t miss Prop Holliday’s best MNF player prop bets for 49ers vs Colts, targeting Jonathan Taylor and Tyler Warren
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