The San Francisco 49ers will be coming off a loss and will once again not have Christian McCaffrey in Week 3 when they face the Los Angeles Rams on the road.

Oddsmakers don't expect those factors to matter.

Per DraftKings Sportsbook, San Francisco opened as a seven-point favorite for the matchup at SoFi Stadium, where the 49ers have never lost a regular-season game.

Factoring into that line will be a hugely difficult start for the Rams, who dropped to 0-2 with a blowout loss to the Arizona Cardinals on Sunday, and suffered another major injury as Cooper Kupp left the game with an ankle injury and was seen in a walking boot afterwards. With fellow wide receiver Puka Nacua already on injured reserve and the Los Angeles offensive line in tatters, the 49ers would appear to have a decided edge over the Rams.

There also hasn't proven to be much of a home advantage for the Rams against the Niners, with San Francisco fans consistently decking SoFi Stadium in red and turning contests in Los Angeles with the Rams into de-facto home games for the 49ers.

As such, it's no surprise a 49er team that, save for the absence of McCaffrey, is healthy, is a touchdown favorite in a game they have dominated in recent years.

Still, after an error-strewn defeat to the Minnesota Vikings in Week 2, the 49ers will know they can't afford to let any complacency creep in against a quarterback in Matthew Stafford who has the high-end ability to keep the Rams in the game despite their many injury issues.

The Rams will be desperate to avoid an 0-3 start but, as the line suggests, the 49ers have no excuse not to get the job done given the highly contrasting states in which these two rosters enter a huge rivalry game.

Kyle Shanahan makes concerning statement about Christian McCaffrey following 49ers loss to Vikings

It’s an increasingly worrying situation.