National Football League

NFL odds: How to bet Colts vs. 49ers, point spread, more

Updated Oct. 20, 2021 4:47 p.m. ET

The slumping San Francisco 49ers hope a bye week hope helps them break a three-game skid as they face the Indianapolis Colts on Sunday.

Here's everything you need to know about the NFL odds on Sunday's matchup between the Colts and 49ers — the point spread, moneyline, total over/under and pick from our betting expert (with all NFL odds via FOX Bet).

INDIANAPOLIS COLTS @ SAN FRANCISCO 49ERS (8:20 p.m. ET Sunday, NBC)

Point spread: 49ers -4 (49ers favored to win by more than 4 points, otherwise Colts cover)
Moneyline: 49ers -200 favorites to win (bet $10 to win $15 total); Colts +170 underdogs to win (bet $10 to win $27 total)
Total scoring over/under: 44.5 points scored by both teams combined

The Colts hold a 26-19 edge in the all-time series, with Indianapolis winning the past four games, including the most recent contest, a 26-23 overtime victory at home on Oct. 8, 2017.

Prior to the Colts four-game win streak, the 49ers beat the Colts seven times in eight games.

The 49ers are 0-6 at home dating back to last season.

It appears Jimmy Garoppolo will return at quarterback for the 49ers, replacing rookie Trey Lance.

Garoppolo suffered a calf injury in early October and has missed the past six quarters, but participated in practice this week and coach Kyle Shanahan said he's optimistic Garoppolo will play. Lance, the No. 3 overall pick out of North Dakota State in April, sprained his knee during Sunday's game and his status is unknown for the Colts game.

In his first NFL start Sunday against Arizona, Lance was 15-for-29 passing for 192 yards and an interception. Lance also ran for 89 yards on 16 attempts, the most by a 49ers quarterback in a game since Colin Kaepernick rushed for 113 yards on 10 carries against the Dolphins in 2016.

Garoppolo has missed 24 of 53 starts since the 49ers made him the highest-paid player in the league before the 2018 season.

Indianapolis' Carson Wentz is 124-for-193 passing (64.2 percent completions) for 1,545 yards (257.5 per game) this season. He has thrown nine touchdowns with one interception.

"I like the Colts here. Carson Wentz is playing well," FOX Sports' Colin Cowherd said. "He's now got multiple games with no interceptions and three touchdowns. The protection has also gotten better, and Jonathan Taylor is a star.

"The Colts are getting healthier, and Wentz is getting more comfortable. He is playing very smart football and limiting the turnovers under Frank Reich. By the way, they did the same thing together in Philly."

The Colts averaged 18.7 points per game in their first three games, and 27.7 points in their past three games.

Turnovers could be a key in this game. The Colts have forced 12 turnovers, fourth-best in the NFL. The 49ers have forced two turnovers, 31st in the NFL.

San Francisco and its opponent have combined to score more than 44 points three times this season.

The Colts are 2-4 and the 49ers 2-3 against the moneyline this season.

Indianapolis’ record against the spread (ATS) is 4-2.

San Francisco has hit the over twice in five games while Indianapolis had hit the over three times in six games.

The 49ers have two takeaways, tied for worst in the league with the Jaguars.

Click here for the latest NFL odds on FOXSports.com and the FOX Sports app for everything you need in the sports betting world.

Pick via FOX Sports' Colin Cowherd: "This is one of my best bets on the board. The better quarterback won 13 out of 13 last weekend. Carson Wentz with Frank Reich is the best quarterback in this game."

PICK: Colts (+4 at FOX Bet) to lose by fewer than 3.5 points or win outright

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