National Football League

Can the Arizona Cardinals save their season in Mexico City?

Updated Nov. 21, 2022 5:33 p.m. ET

The Arizona Cardinals gained new life with a win over the defending Super Bowl champions last week, a 27-17 victory against the Los Angeles Rams at SoFi Stadium.

However, the 4-6 Cardinals still have an uphill climb to make the postseason. Even worse, they play one of the hottest teams in the NFL, the San Francisco 49ers, in Mexico City on Monday Night Football, probably without the services of Kyler Murray.

Arizona's starting quarterback is listed as questionable due to a lingering hamstring injury. However, according to reports, backup Colt McCoy will get his second straight start against the surging 49ers.

McCoy played efficient football for Arizona last week, completing 26 of 37 passes for 238 yards and a touchdown. He suffered a knee injury during the game but practiced all week and has been cleared to play against San Francisco.

"Colt just being in so many different offenses and seeing so many different defenses, the game has really slowed down for him," Arizona coach Kliff Kingsbury said. "Particularly, when he gets to the line pre-snap, he can see what's coming. He knows different looks. He studies a ton of film. There are certain guys that just have that knack. And he's one of those guys that can pick it up pre-snap and know what the defense is about to do."

The Cardinals will also be without tight end Zach Ertz, who suffered a season-ending knee injury last week that required surgery. However, they should get back receiver Marquise "Hollywood" Brown from a foot injury that forced him to miss four games.

If DeAndre Hopkins can play after missing practice time this week because of a hamstring injury, it will be the first time that Brown and Hopkins play together in a regular-season game this year.

Losers of four of their past six games, the Cardinals need all the healthy players they can get in facing the 49ers. San Francisco is 5-4 but has won two in a row and four of its past six games. Arizona still has an outside shot of catching San Francisco for the final wild-card spot in the NFC, but the Cardinals need to start stacking wins.

"It's not over," Murray said. "Obviously, the season has not gone how we've wanted it. But we're still in it and the season is not over. We know this team is talented enough to go on a run, and that's the mission. That's the mentality right now."

The Cardinals and the 49ers took two different paths to get ready for the high altitude in Mexico City. Arizona chose to train at the team's facility this week and leave for the game Saturday.

San Francisco traveled to Colorado Springs, Colorado, practicing at the Air Force Academy in a higher altitude to prepare for what they will face in Mexico City.

"It was strictly because of altitude," San Francisco coach Kyle Shanahan told NBC Sports Bay Area. "We've had to play in Denver before, but up here in Colorado Springs it's 2,000 feet high almost, which is exactly how Mexico City is. So, that is a big deal."

The two teams were involved in the first regular-season game played outside the United States on October 2, 2005 in Mexico, a 31-14 victory for the Cardinals. However, the 49ers are 3-0 in the NFC West this season and have not given up a point in the second half of the team's last two games defensively.

McCoy can lean on recent history for some confidence. He started in Arizona's win over San Francisco last season, a 31-17 victory over the 49ers in which the Texas product completed 22 of 26 passes for 249 yards and score.

The Cardinals swept the season series against San Francisco last season and have won seven of the last 10 games since Shanahan took over as the team's head coach in 2017.

Arizona is a heavy underdog in this one. Even though the Cardinals are the home team, they will feel like they are on the road, with a large presence of San Francisco fans expected at Estadio Azteca.

"We're just trying to play good ball out there," Cardinals defensive lineman J.J. Watt said. "We're trying to get takeaways, trying to get sacks and trying to do whatever we can to get our team to win. We try to improve every single week and the law of how practices and game work is, if you keep working at it, you're going to keep getting better."

Eric D. Williams has reported on the NFL for more than a decade, covering the Los Angeles Rams for Sports Illustrated, the Los Angeles Chargers for ESPN and the Seattle Seahawks for the Tacoma News Tribune. Follow him on Twitter at @eric_d_williams.