The San Francisco 49ers were routed by the Green Bay Packers in Week 12 in another big blow to their playoff hopes, and the oddsmakers don't expect things to get any better in Week 13 at the Buffalo Bills.

San Francisco is now 5-6 after slumping to a 38-10 defeat to the Packers without Brock Purdy, Nick Bosa and Trent Williams.

Next up is a meeting with a Bills team coming off a game in which they handed the Kansas City Chiefs their first defeat, a primetime game for which they will hope to have Purdy and Co. back in the fray. 

But the oddsmakers don't appear to have any confidence in the 49ers to hang with Buffalo.

Indeed, the 49ers opened as 6.5-point underdogs against the Bills, per Oddstrader.

It is the first time the 49ers have been more than a six-point underdog since the final game of the 2020 season, when the Seattle Seahawks were seven-point favorites for a game played in Arizona.

San Francisco covered the spread on that occasion, losing 26-23, so perhaps being in an unfamiliar and unwanted position can be a good omen for the 49ers.

But it is fitting that the last time the 49ers were such heavy underdogs was in the nightmare 2020 campaign in which injuries ruined their hopes of competing. The 49ers only have themselves to blame this year, but a season that looks to have all the hallmarks of a Super Bowl hangover shares a lot of similarities with their dreadful 2020.

Unless the 49ers can find a way to turn things around, this campaign will also end before the playoffs, just as it did for San Francisco in the first season of the decade.

49ers had new problems against the Packers, but failure to shake off same old ones likely doomed their season

The injuries weren’t the biggest issue.