Arizona Cardinals (4-6) vs. San Francisco 49ers (5-4) in Mexico City

Typically the rule of thumb is to take the favorite in neutral site international games, as the better team tends to have a bigger international fan base and tends to be better suited to play in a weird situation like this, leading to the favorite covering at a 62.8% rate (27-16 ATS) all-time. The 49ers are 8-point favorites, but that’s probably not high enough. The Cardinals are 4-6, which isn’t bad, but they have needed a +5 turnover margin (5th best in the NFL) just to sustain that mediocre record and turnover margins are not predictive week-to-week. Meanwhile, in terms of schedule adjusted efficiency, which is much more predictive, the Cardinals rank just 25th, four points below average.

My roster rankings have the Cardinals even worse, 8.5 points below average, due to injuries, primarily on the offensive line, with arguably their top-4 offensive linemen left tackle DJ Humphries, left guard Justin Pugh, right guard Will Hernandez and center Rodney Hudson all out. Starting quarterback Kyler Murray is also questionable and, while backup Colt McCoy is a decent replacement, he doesn’t give this offense the same upside as Murray, especially behind an injured offensive line and, even if Murray plays, he might not be quick as mobile this week, due to his lingering hamstring injury, also a problem behind a banged up offensive line.

The 49ers, meanwhile, are much better than their 5-4 record, ranking 8th in point differential at +35 and 5th in schedule adjusted efficiency, five points above average. The 49ers are also healthier now than they were earlier in the season. Wide receiver Deebo Samuel, tight end George Kittle, and left tackle Trent Williams are all among their best offensive players and all missed time earlier this season, but all three have returned, a huge boost for an offense that also got a big boost from adding Christian McCaffrey in a trade a few weeks ago. The 49ers’ defense also got healthier out of the bye, with linebackers Dre Greenlaw and Azeez Al-Shaair and safety Jimmie Ward returning to action last week. My calculated line has the 49ers favored by 11.5 on a neutral site and, in a good spot as well, I think the 49ers are bettable.

San Francisco 49ers 28 Arizona Cardinals 16

Pick against the spread: San Francisco -8

Confidence: Medium