49ers vs. Buccaneers Prediction, Odds, Spread, Injuries, Trends for NFL Week 6

Iain MacMillan | Oct 7, 2025

The 49ers are road underdogs against the Buccaneers in Week 6 of the NFL season. / Kim Klement Neitzel-Imagn Images

The San Francisco 49ers and Tampa Bay Buccaneers are set to face each other in an NFL Week 6 battle between two 4-1 teams.

Both teams have been battling some significant injuries this season, but the 49ers have had worse luck than arguably any other team in the NFL. Their quarterback, top three receivers, and a handful of defensive players missed their Week 5 game, and we're yet to find out if any will return for Week 6.

Let's take a look at where the odds stand right now and then I'll break down my best bet.

49ers vs. Buccaneers Odds, Spread, and Total

Odds via FanDuel Sportsbook

Spread

• 49ers +3 (-115)
• Buccaneers -3 (-105)

Moneyline

• 49ers +130
• Buccaneers -154

Total

• OVER 47.5 (-108)
• UNDER 47.5 (-112)

49ers vs. Buccaneers How to Watch

• Date: Sunday, Oct. 12
• Game Time: 4:25 pm ET
• Venue: Raymond James Stadium
• How to Watch (TV): CBS
• 49ers Record: 4-1
• Buccaneers Record: 4-1

49ers vs. Buccaneers Betting Trends

• 49ers are 4-10 ATS in their last 14 games
• The OVER is 6-2 in the 49ers' last eight games
• The OVER is 4-1 in the 49ers' last five road games
• 49ers are 6-13 ATS in their last 19 games vs. NFC opponents
• The OVER is 14-6 in the Buccaneers' last 20 games
• Buccaneers are 4-2 ATS in their last six games vs. NFC West opponents
• Buccaneers are 2-8 ATS in their last 10 games played in Week 6

49ers vs. Buccaneers Injury Reports

49ers Injury Report

• Jordan Watkins, WR - Questionable
• Brock Purdy, QB - Questionable
• Ricky Pearsall, WR - Questionable
• Jauan Jennings, WR - Questionable
• Robert Beal Jr., DE - Questionable
• Malik Mustapha, S - Out
• George Kittle, TE - IR
• Nick Bosa, DE - IR
• Brandon Aiyuk, WR - Out

Buccaneers Injury Report

• Benjamin Morrison, CB - Questionable
• Christian Izien, S - Questionable
• Bucky Irving, RB - Questionable
• Jamel Dean, CB - Questionable
• Mike Evans, WR - Out

49ers vs. Buccaneers Key Player to Watch

• Baker Mayfield, QB - Tampa Bay Buccaneers

Baker Mayfield has catapulted himself into the MVP conversation through the first five weeks. He's sitting at +950, behind only Josh Allen and Patrick Mahomes. He has been the main reason the Buccaneers are sitting at 4-1 despite dealing with a plethora of injuries. Let's see if he can further build on his impressive 2025 campaign on Sunday.

49ers vs. Buccaneers Prediction and Pick

In this week's edition of the Road to 272 Bets, I broke down why I'm taking the points with the 49ers:

The Tampa Bay Buccaneers keep winning, despite the advanced metrics not liking this team. They're just 18th in the NFL in DVOA this season. Their offense has been good, but their 20th ranking on defense and 31st ranking on special teams hurts them.

People haven't talked about how bad their secondary has been this season. They rank 27th in opponent dropback EPA, 31st in opponent dropback success rate, and 21st in opponent yards per pass attempt, giving up 6.8 yards per throw.

That's a dream scenario for a Kyle Shanahan offense that can scheme up a game plan to torch a bad secondary. We're going to hope that the 49ers get some good injury news this week, and if they do, this 49ers +3 bet is going to look great come Sunday.

Pick: 49ers +3 (-115) via FanDuel

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