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49ers vs. Cardinals: 5 keys to winning in NFL’s return to Mexico City

AIR FORCE ACADEMY, Colo. – The 49ers are gambling that, after a chilly week here, their lungs are ready for the 7,218-foot summit that is Estadio Azteca, site of Monday night’s game in Mexico City against the Arizona Cardinals.

High-altitude acclimation is not all they encountered.

Tests in mental fortitude arose thanks to unexpected, bone-chilling weather and snow showers, the opposite of what awaits when they fly today south of the border.

“It’s been an interesting trip,” defensive end Nick Bosa said Friday. “It’s definitely testing our fortitude and our ability to stay positive.”

Altitude. Fortitude. Even attitudes came into play as the 49ers’ prepared for a possible third straight win, in a much southern latitude.

A month removed from the team’s West Virginia layover, Jimmy Garoppolo agreed this was a peculiar trip, saying: “Nick worded it pretty well.” Garoppolo added that the altitude indeed tested teammates, that “guys were sucking air a little bit. But it’s good for us. We’re going to play in that Monday.”

They’ll play in a pro-49ers crowd, projected as much as 82 percent in their favor, which would be about 71,500 of the 87,523 capacity, per Vivid Seats’ fan forecast. Say hello, or hola, to Levi’s Sur.

“I’ve heard there’s a lot of Mexican 49ers fans, so it should be pretty good,” Bosa added. “The stadium looks really cool. It should be loud and fun.”

Here are five ways the 49ers can win and have more fun than their 2005 visit, when they lost to the Cardinals 31-14 in the NFL’s first regular-season international game:


One of the NFC West’s best matchups features 49ers tight end George Kittle and Cardinals safety Budda Baker. Both have made big-time plays, and Kittle has come away injured from a couple of interactions.

“He’s the first that’s always there to tackle me if I have the football,” Kittle said. “… He’s one of  my favorite guys to go against because his effort on tape.”

Nor does Kittle, unless injured. He got hurt in a 2019 Halloween win at Arizona, but he also beat Baker for a touchdown that game. In the 2020 opener, Baker’s low hit on a jumping Kittle resulted in a knee inury that sidelined the 49ers’ star the next two games.

Baker was called one of the NFL’s best players by 49ers defensive coordinator DeMeco Ryans. But Baker is battling an ankle injury, one of many health issues crippling the Cardinals this season.

Kittle had just one catch – albeit a sparkplug — in last Sunday’s win over the Los Angeles Chargers. “I tell Jimmy on the sidelines all the time, I always tell him, I’m open, I’ve got one-on-one coverage, I’m available, just throw me the ball if you need me,” Kittle said.

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If this turns into a pass-oriented shootout, the 49ers’ defense will have its hands full. The Cardinals could have DeAndre Hopkins (hamstring; questionable) and Marquise Brown (short-term injured reserve) together for the first time this season, not to overlook the presence of A.J. Green and Rondale Moore, the latter of whom has averaged eight catches for 85 yards the past three games.

Hopkins, after starting the season on a six-game suspension for a performance-enhancing drug violation, isn’t shy about demanding the ball, as HBO’s “Hard Knocks” documented in a recent sideline exchange he had with Kyler Murray. Hopkins caught 14 of 16 targets for 151 yards in a 2020-opening win at the 49ers.

The 49ers’ secondary will have their lungs tested the most against that corps, and starting cornerback Charvarius Ward missed practices this week while excused for a family matter.

Is the 49ers’ receiving corps better? Brandon Aiyuk is enjoying the best stretch of his 2 ½-season career. Deebo Samuel is healthy. Jauan Jennings is a third-down menace. And Christian McCaffrey is at the ready from the slot or backfield, as is Kittle (see: above item vs. Baker).


The 49ers expect Murray to return from a hamstring injury that kept him out of the Cardinals’ last game, a win over the Los Angeles Rams in which Colt McCoy won in his place. Murray is listed as questionable.

What do they actually expect from Murray? Speed. Elusiveness. Or, simply, the mobility they’ve struggled to contain with their aggressive pass rush.

Perhaps just as hazardous to the defense’s health is how they’ll attack Murray on the run. Dre Greenlaw got ejected before halftime last Sunday for his helmet-to-helmet hit on Chargers quarterback Justin Herbert. Murray’s 5-foot-10 frame isn’t easy to nab, but Nick Bosa is the 49ers’ best shot at capturing him and adding to a 9 ½-sack total that is the NFL’s second-best.

Murray doesn’t have to run to beat the 49ers, and that hamstring issue could force him to play more from the pocket. He had seven carries for 1 yards in last October’s 17-10 win over the 49ers, in Trey Lance’s first career start as the Niners’ quarterback.

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