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2022 NFL season: Four things to watch for in 49ers-Cardinals game in Mexico City on 'Monday Night Football'

  • WHERE: Estadio Azteca (Mexico City)
  • WHEN: 8:15 p.m. ET | ESPN, ESPN Deportes, NFL+


Coming off of victories against the Chargers and the Rams, respectively, the 49ers and the Cardinals face off Monday night to close out Week 11 with an NFC West rivalry in the Estadio Azteca, the historic Mexico City stadium that has hosted two World Cup finals (1970 and 1986). This will be the fifth and final international game played in 2022, tying 2017 and '19 for most in a single season.


Monday night's 49ers-Cardinals clash is a rematch of the first NFL regular-season game played in Mexico, a 31-14 comeback win by Arizona in Week 4 of the 2005 campaign. In that contest, the second-highest-attended regular-season game in NFL history (103,467), the Cardinals fell behind 14-0 in the first quarter before scoring 31 unanswered points to earn the win.


One of the favorites for Comeback Player of the Year in NFL.com’s midseason predictions, Christian McCaffrey, is ready to face Arizona’s defense and shine. He needs one receiving TD to become the sixth player in NFL history with 20-plus rush TDs and 20-plus receiving TDs over their first six NFL seasons, joining Alvin Kamara, Austin Ekeler, Brian Westbrook, Chuck Foreman and Hall of Famer Lenny Moore.


Here are four things to watch for when the 49ers face the Cardinals on Monday Night on ESPN:


  1. NFL returns to a lucky spot. Six years after the first MNF game ever played outside of the United States, and three years after the last game played in Mexico, the 49ers and Cardinals will join the Raiders (1-1) as the only teams to play multiple games in Mexico. And this location has brought luck to the teams that have visited it: Four of the last six teams to play a regular-season game in Mexico City have reached the playoffs and the two most recent winners (Chiefs, 2019; Patriots, 2017) both earned trips to the Super Bowl that season. Will the trend continue this year?
  2. 49ers' star-studded offense faces a struggling Cardinals defense. The 49ers' offense is ranked ninth in the league, and with the addition of McCaffrey, it now has an excess of offensive playmakers. All-Pro Deebo Samuel has a career average of 15.0 yards per reception and 6.6 yards per carry, and McCaffrey is the only player in NFL history to average 50 rushing yards and 50 receiving yards per game. Talk about dual threats. Even though Arizona’s defense ranks ninth against the run, it has serious issues when it comes to scoring (30th) and red zone (28th) defense. Arizona will have to find ways to limit big plays, hold San Francisco to field goals and control the clock.
  3. Which team will get more out of their star playmakers? McCaffrey has had a profound impact on the 49ers' offense in a short amount of time, helping the team win two straight games and making an already dangerous running attack that much scarier. The 49ers, known for their ability to rush outside the tackles, have seemingly flipped the script this season, leading the league in first downs over expected (9) rushing inside the tackles, per Next Gen Stats. McCaffrey has played his part here, producing a far higher average rushing inside (5.6 yards) than outside (3.0) since joining the Niners in Week 7. The Cardinals, of course, have their own superstar in DeAndre Hopkins, who has been incredibly productive since rejoining the team, following his six-game suspension to start the year. He leads all WRs in receptions (36), ranks third in receiving yards (396) and has two receiving TDs since his Week 7 debut. The Cardinals' offense raised its points per game from 19 to 29 after Hopkins' return. Although the five-time Pro Bowler is listed as questionable for Monday's matchup with a hamstring injury, coach Kliff Kingsbury described the issue on Friday as "maintenance."
  4. The Cardinals offense with and without Kyler Murray. The latest Cardinals injury report listed Kyler Murray as questionable for Monday's game due to his hamstring, but the star QB will miss his second straight game. Arizona will again turn to veteran backup Colt McCoy (3-1 as the Cardinals' starter), who threw for 238 yards and a touchdown with a 96.5 passer rating in the team's Week 10 victory against the Rams. The Cardinals scored 27 points with McCoy under center, something they failed to do in seven of the last nine games that Murray started. Although Kingsbury and Co. would surely love to have had Murray on the field, McCoy's recent success allows the team to be even more cautious in not rushing their QB1 back too soon.