A battle near the top of the NFC is a marquee matchup in NFL Week 6. The San Francisco 49ers cross the country for a clash with the Tampa Bay Buccaneers on Sunday.
The banged-up Niners have enjoyed a much-needed mini bye after winning last Thursday. That break allows San Francisco to get some weapons back on this offense, just in time for a potential shootout in the Sunshine State.
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My 49ers vs. Buccaneers predictions are eyeing the San Francisco offense to have its best day with my NFL picks for Sunday, October 12.
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49ers vs Buccaneers prediction
49ers vs Buccaneers Best bet: 49ers team total Over 22.5 (-120)
Injuries have hampered Kyle Shanahan’s offense in the opening five weeks, and this attack will still be missing pieces in Week 6.
However, after stealing a win over the rival L.A. Rams last Thursday, the San Francisco 49ers are optimistic the extended break can get receiver Juan Jennings back on the field and perhaps give Ricky Pearsall time to recover.
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The 49ers are still likely without quarterback Brock Purdy for this trip to Tampa. That said, Shanahan’s offense has always had a plug-and-play approach at QB, and Mac Jones’ efforts in Week 5 are even more proof of that.
Jones has been great filling in for Purdy the past three games, leading the Niners to victory in each outing. His most recent appearance against the Rams defense was especially impressive, with Jones throwing for 342 yards and two touchdowns in a 26-23 overtime win.
This matchup with the Tampa Bay Buccaneers presents an opportunity to build on that offensive momentum. Tampa Bay has been among the best defenses against the run, but is equally as poor versus the pass.
It sits 31st in opponent success rate per dropback, 29th in EPA allowed per dropback, and 25th in pass defense DVOA at FTN. The Bucs have watched opposing quarterbacks boast an average passer rating of 105.0 and allowed 16 passing plays of 20-plus yards.
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Injuries to top corners Jamel Dean and Zyon McCollum, as well as questionable designations to their backups, compound that weakness.
While the Niners have scored 23 points or more only twice in regulation through five games, the offense hasn’t been as bad as the scoreboard would lead you to believe. The 49ers are No. 5 in success rate per play and 10th in offensive DVOA but can’t seem to crack the goal line.
San Francisco sits 28th in touchdown rate inside the red zone (42.11%), including going 3 for 8 inside their opponents’ 20-yard line the past two games. Luckily for Shanahan & Co., the Bucs are hemorrhaging points.
Todd Bowles’ team has given up a total of 93 points in the last three outings and enters Week 6 with foes feasting inside the red zone, to the tune of a 71.43% TD rate (29th). In fact, during that three-game span, the Bucs have buckled for a touchdown on nine of their 10 red-zone stands.
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49ers vs Buccaneers same-game parlay
The Niners can build on the momentum of Week 5 and take poor passing defense from Tampa Bay.
San Francisco is coming off a mini bye and takes on a Tampa team coming off an emotional road win last Sunday.
Bourne has stepped up with injuries in the receiving corps and has chemistry with Jones, going back to their New England days.
49ers vs Buccaneers SGP
- 49ers team total Over 22.5
- 49ers +3.5
- Kendrick Bourne anytime TD
Our big-ticket SGP: TEASER
Jones gets some receiving weapons back against a Tampa Bay team giving up a ton of points the past three weeks. San Francisco’s offense won’t stall out against the Bucs’ bad red zone defense. Bourne drew 11 targets last week and will have an opportunity to get in the end zone Sunday.
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49ers vs Buccaneers SGP
- 49ers team total Over 22.5
- 49ers +3.5
- Kendrick Bourne anytime TD
- Cade Otton anytime TD
49ers vs Buccaneers odds
- Spread: 49ers +2 | Buccaneers -2
- Moneyline: 49ers +108 | Buccaneers -127
- Over/Under: Over 47 | Under 47
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49ers vs Buccaneers trend to know
Kyle Shanahan is 18-13 ATS as a road underdog in the regular season during his time as San Francisco’s head coach (since 2017). Find more NFL betting trends for 49ers vs. Buccaneers.
How to watch 49ers vs Buccaneers
| Location | Raymond James Stadium, Tampa, FL |
| Date | Sunday, October 12, 2025 |
| Kickoff | 4:25 p.m. ET |
| TV | CBS |
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