Every NFL team wants to believe they've got a chance each week. Any given Sunday, right? Wrong.
There are a handful of teams each week who simply don't have the talent to keep up with the teams they're going up against. There are a number of teams in the NFL dealing with too many injuries, bad coaching, too much youth, or a combination of factors that will ultimately lead to losses in Week 5 of the 2025 NFL season.
Although anything can happen, and trying to "guarantee" something in the NFL is a foolish thing to practice on a regular basis, we're pretty sure these four teams are going to lose this week. What could go wrong?
NFL Predictions: 4 teams guaranteed to lose in their Week 5 matchups
1. San Francisco 49ers (@ Rams, Thursday night)
Wait a second...Isn't this a rivalry game being played between two evenly-matched 3-1 teams?
Absolutely not. There is nothing "evenly matched" about the 49ers and Rams right now, and it's a tough reality for a team like the 49ers to face. The 49ers are absolutely reeling right now and are losing the war against not the injury "bug", but the Injury Warlord itself.
Nick Bosa is done for the year, and the 49ers are already without Brandon Aiyuk. Against the Rams, they'll be missing Brock Purdy (again) as well as Ricky Pearsall and Jauan Jennings.
The talent discrepancy between these two teams gives the Rams a massive margin for error. It would take a herculean upset for the 49ers to pull this one off, especially on a short week.
2. Cincinnati Bengals (vs. Lions, Sunday)
The Cincinnati Bengals are fortunate to be 2-2 right now instead of 1-3, and it won't be long until we're wondering how they got that second win of the year against the Jaguars when Joe Burrow went down with an injury.
The Bengals didn't run a single play beyond midfield in Week 4 against the Denver Broncos after their very first drive of the game. They had nine total first downs and are now facing off against an extremely well-oiled machine of an offense in the Detroit Lions.
The Lions are 10.5-point favorites heading into the week, which feels super generous toward the Bengals. In a battle of jungle cats, the Lions are going to prove themselves to be king once again.
3. Tennessee Titans (@ Cardinals, Sunday)
The Tennessee Titans may have the worst head coach in the NFL currently in Brian Callahan. They should be in line for a huge dump of veterans at the NFL trade deadline.
It would be shocking if this team didn't get worse before it got better, which is saying something considering Cam Ward's assessment of where things are at after Week 4.
#Titans QB Cam Ward is clearly frustrated with the lack of production on offense starting with himself. "If we keep it a buck right now, we ass." pic.twitter.com/ApQzABZBG2
— TURRON DAVENPORT (@TDavenport_NFL) September 28, 2025
Now, the Titans have to face off against the Arizona Cardinals in Week 5. It may not seem like that bad of a draw for them, but the Cardinals are coming off of a loss and are playing at home with extended rest.
4. New England Patriots (@ Bills, Sunday night)
Another team with a really tough draw this week is the New England Patriots. The Patriots absolutely. blew out the Carolina Panthers in Week 4, but the Panthers are going to look like a college team compared to the Buffalo Bills.
The Bills are absolutely hearing the noise about the performance of their defense so far this season under coordinator Bobby Babich. They had a bit of a struggle last week against the New Orleans Saints, but this BIlls team has such a significant margin for error, they still won by 12 points.
Buffalo is favored by 8.5 points in Week 5 and it'll be interesting to see if Drake Maye and the Patriots can keep it under double digits. You want to buy the Pats after their blowout win and Maye's performance in Week 4, but they've still got a long way to go before they get to Buffalo's level.
We'll see how significant of a step they can take under the lights of primetime.