Colts vs. 49ers Point Spread: NFL Week 7 Odds, Prediction

Payton Matthews | Updated Oct 19, 2021

Coming off a bye week, can the rested San Francisco 49ers gain some momentum at home against Indy?

October 24, 2021, 8:20 PM ET
Levi's Stadium
Pointspread +3 -110
Moneyline +137
Over / Under o +41.5


Betting Action


Pointspread -3 -110
Moneyline -165
Over / Under u +41.5


Betting Action


The San Francisco 49ers have a quarterback question as they enter Sunday night’s NFL Week 7 home matchup against the Indianapolis Colts.

The Niners are 3.5-point favourites to win on the NFL odds, with a total of 45 points.

NFL Point Spread and Betting Analysis

The Colts and 49ers both took different routes to finding a franchise quarterback this off-season. Indianapolis lost veteran Philip Rivers to retirement and opted to trade draft picks to Philadelphia for Carson Wentz, the No. 2 overall pick in the 2016 draft. How well/often Wentz plays will determine whether the Colts have to hand over a first-round pick next year. The jury is still out on him.

San Francisco traded a king’s ransom in their 2021 first-round pick (12th overall), first-round picks in 2022 and 2023 and a 2022 third-rounder to Miami ahead of this year’s draft to move up from No. 12 to No. 3 overall to take talented but raw North Dakota State quarterback Trey Lance even though Jimmy Garoppolo had led the Niners to the Super Bowl as recently as the 2019 season. However, Jimmy G regressed in 2020 and has had trouble staying healthy.

Dating to their Baltimore days, the Colts are 26-18 all-time against the 49ers – they have never met in the playoffs. Indy won its fourth straight in the series in the most recent meeting in 2017 by a score of 26-23 in overtime in Indianapolis. The quarterbacks that day were Brian Hoyer for the Niners (now a backup with New England) and Jacoby Brissett for the Colts (now a backup with Miami).

The road team is 4-1 against the spread in the past five meetings.

Indianapolis Colts

Few teams since training camp have been hammered by injury quite like the Colts, so it’s perhaps not too surprising the team is off to a disappointing 2-4 start. It did play a very tough first five games before getting a breather this past Sunday and blasting terrible Houston 31-3. Head coach Frank Reich wants his offence to revolve around second-year running back Jonathan Taylor and it did vs. the Texans as he had 145 yards rushing and two scores on 14 carries. QB Carson Wentz played mistake-free football and threw for two scores. Speedy wideout Parris Campbell caught a 51-yard TD pass but suffered what is thought to be a serious foot injury. Fellow wideout T.Y. Hilton made his season debut Sunday after missing the first five games with an injury and had four catches for 80 yards. He did suffer a minor quad injury.

This is a very good defence when everyone is healthy, led by maybe the best middle linebacker in the NFL in Darius Leonard. He forced one of three turnovers vs. the Texans. The Colts are 7-2 ATS in their past nine on the road.

San Francisco 49ers

San Francisco comes off its bye week and it came at a good time with quarterbacks Jimmy Garoppolo and Trey Lance and a few running backs, among others, banged up. Coach Kyle Shanahan has said Garoppolo is the team’s starter if healthy, but he wasn’t available in a 17-10 loss at Arizona in Week 5. Lance made his starting debut and was 15-for-29 for 192 yards with a pick but led the team with 89 yards on 16 carries but suffered a knee injury (not overly serious). Jimmy G was at practice Monday and Lance wasn’t so that could be telling.

Every 49ers game has been decided by eight points or fewer. The team could be 5-0 … but also 0-5. The defence has just two takeaways, second-fewest in the NFL. San Francisco is 1-5 ATS in its past six at home.

NFL Prediction: Who Will Win Colts vs. 49ers?