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It started with a Trenton Cannon knee injury on the opening kickoff.

Then Taylor Lewan went down with a knee injury of his own on the Titans’ first offensive play from scrimmage, followed by a hip injury to edge rusher Bud Dupree near the end of the first half.

And just like that, the Titans were down three players and down 17-7 by halftime.

The second half wasn’t much better. In fact, it was worse. 

Stefon Diggs hauled in two of his three touchdown grabs and Matt Milano’s 43-yard pick-6 put an exclamation point on the Buffalo Bills' 41-7 blowout of the Titans Monday night at Highmark Stadium in Buffalo.

“We got our asses kicked, plain and simple,” Titans head coach Mike Vrabel said. “They outcoached us, they outplayed us, and that’s the definition of it. We’re going to get back to work and figure out a way to win a football game.”

It marked the worst loss of the Vrabel era, and it was the Titans’ worst loss since a 38-10 outing against the Indianapolis Colts on Nov. 18, 2018. Tennessee’s 187 yards of total offense was also its lowest since a 21-0 loss to the Baltimore Ravens on Oct. 14, 2018, when the Titans mustered just 106 total yards.

Ryan Tannehill recorded the worst passer rating (32.7) of his career and the second-fewest passing yards (117) since becoming the Titans starter in 2019, and his 11 completions are tied for the second-fewest of his Titans’ tenure and the third-fewest of his career.

“It’s brutal,” Tannehill said. “I haven’t been a part of a whole lot of games like that. Brutal night. We had a lot of football out in front of us. So, we have to turn the page quickly on this one and get ready to go next week on a short week now. This one’s tough to swallow, but we can’t sit around and have the woe-is-me attitude.”

The blame certainly doesn’t rest completely on Tannehill. The offensive line struggled with Lewan out. Aaron Brewer got pushed around, and Von Miller toyed with Dennis Daley on a few occasions.

Derrick Henry’s 25 yards rushing was the third-fewest since he became the team’s starter in 2018, and his 1.9 yards per carry was tied for his lowest output over his last 56 regular season games.

And while Treylon Burks (4 receptions, 47 yards) and Robert Woods (4 receptions, 39 yards) didn’t look completely incompetent, Diggs (12 receptions, 148 yards, 3 TDs) outperformed the entire Titans receiver group (12 receptions, 123 yards) by himself.

Many said last week’s 21-20 loss to the New York Giants was Todd Downing’s worst game as Tennessee’s play caller. That was, of course, before Monday night’s debacle happened.

Then there was the defense, which surrendered over 100 yards rushing for the second straight game and allowed Josh Allen to pick them apart to the tune of 317 yards and four touchdowns. He was sacked just once.

The MVP frontrunner picked on an inexperienced secondary that was without top cornerback Kristian Fulton. While the Titans invested high draft picks in Caleb Farley and Roger McCreary, they both showed on Monday that they’re a long way off from being starting caliber defensive backs.

“I showed up here ready for a fist fight,” Farley said, via ESPN’s Turron Davenport. “I gave up an X play on a fade; I can’t get it back. I got punched in the mouth, and I was trying to just get some punches back in. It just didn’t work out that way. So, I don’t want to speak too much [more] on that.”

Follow Michael Gallagher on Twitter @MGsports_