The first time the San Francisco 49ers and Arizona Cardinal tangled this season the visitors were missing their starting quarterback at State Farm Stadium. This week, the visitors are again the team with the missing quarterback.

Four weeks ago, Jimmy Garoppolo was sidelined with a calf injury when the 49ers battled the Cardinals in an NFC West Division matchup. Tomorrow, the Cardinals will be without Kyler Murray as they visit Levi’s Stadium. Four weeks ago when the 49ers were forced into an early insertion to the starting role for rookie Trey Lance, the Cardinals took advantage and won, 17-10.

With Colt McCoy running the Cardinals offense on Sunday, we expect a similar positive outcome for the 49ers.

Just a week ago, the 49ers were mired in a four game losing streak and behind two of the best teams in football in the NFC West, the Cardinals and Los Angeles Rams. It was a peek into the abyss as far as any hope for the 2021 season was concerned. The Niners road win over the Chicago Bears was the first step towards redemption, and the Cardinals first loss of the season suffered at home against the Green Bay Packers also sparked a potential comeback for a team that came into the season with legitimate Super Bowl aspirations.

Murray is seen as critical to the Cardinals success and his loss shifted the point spread on this game five points. The Cardinals were a 2½ point favorite before it was learned he would not play as evidenced in the line shifting to the 49ers favored by 2½ points. The Cardinals are still shopping the idea that Murray will play this week, an obvious ploy to force the 49ers to prepare for two quarterbacks.

While Kyle Shanahan is not looking for my advice, I will offer it anyway. Don’t spend any time preparing to face Murray even while the Cardinals say the option is open. The guys that know more than anyone, it is their business to know, declared Murray out with the drastic line shift on Thursday.

In his absence, the Cardinals will start Colt McCoy, a 12-year veteran certainly capable of putting together a winning effort while supported by a motivated squad.

Teams missing a key play routinely have a motivational spike that enhances their performance.

Still, that spike runs smack into the possibility of the 49ers getting back into the hunt in the NFC West, while a loss dooms them after only half the regular season has been played.

If this season turns for the 49ers, if the insertion of George Kittle back into the offense and a healthy Garoppolo create magic, the 49ers will look at their home loss two weeks ago against the Indianapolis Colts as rock bottom. Sunday’s win over the Cardinals being the second of a three step process to get back into the thick of the division hunt.

It started with their victory last week at Soldier Field, and next Sunday, the 49ers host the Los Angeles Rams. Back-to-back wins at Levi’s Stadium would pull the 49ers to within at least two games of the front-running Rams.

First things first, the easier of these two challenges is Sunday’s revenge contest against the Cardinals.

Qoxhi Picks: San Francisco 49ers (-2½) over Arizona Cardinals