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With a few major programs already suffering early losses, Week 3 serves as make-or-break time for hopeful College Football Playoff contenders.

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While Week 1 of the college football season provided a five-day stretch of excitement—from Tennessee needing overtime to avoid an upset against Appalachian State to Florida State storming back from a big deficit to outlast Ole Miss—this week will present several teams an opportunity to notch a key win that would further their efforts of earning a bid to the College Football Playoff.

The action kicks off Thursday night when No. 6 Houston heads to Nippert Stadium to take on Cincinnati, in what many college football pundits have described as the Big 12 Expansion Bowl. Of course, the Cougars are looking for more than a second consecutive New Year’s Six bid at this point. Head coach Tom Herman has a squad that could flirt with a CFP berth, especially if Oklahoma and Louisville—the Cougars’ main attractions on their schedule—finish the season strong and help out in terms of strength of schedule.

All eyes will be on Louisville and Papa John’s Cardinal Stadium early Saturday morning when a prime ACC Atlantic division matchup takes place between No. 2 Florida State and the No. 10 Cardinals. Bobby Petrino’s star quarterback Lamar Jackson has created a very early Heisman Trophy buzz for himself, and he takes a major step up in competition against the Seminoles, although Jimbo Fisher’s squad will be without star safety Derwin James. While the FSU-Clemson matchup in October was circled on all the offseason calendars, the Seminoles will have a major fight on their hands against a team looking to become an annual league contender like the ‘Noles and Tigers.

Already with a loss to FSU, No. 19 Ole Miss looks to notch its third consecutive win over No. 1 Alabama roughly two years after Katy Perry made her presence felt on The Grove. The Rebels will need to play a near-perfect game if they want to accomplish the rare feat against Nick Saban’s squad. According to the college football research team at Pro Football Focus, Alabama has pressured opposing quarterbacks 35 times already this season. Under such duress after two games, Kelly is completing just 31.6 percent of his throws. We saw him rattled in the second half of the season opener in Orlando against FSU’s defense. The ‘Bama ‘D’ does not seem to have taken a step back, while the Ole Miss ground game leaves a lot to be desired. It could be a long day for the Rebels if their up-tempo offense is not clicking.

With so many major programs facing must-win situations already, it would be fitting for a “Desperation Saturday” theme to be tossed around. Following an opening loss to Texas in Austin, No. 18 Notre Dame has no room for error—especially with a schedule that looks solid but isn’t quite as strong as in years past. The Irish don’t have Florida State, Clemson or Louisville from the ACC this year, which would have helped its strength of schedule cause.

But, first thing’s first. Notre Dame must get past No. 12 Michigan State this week. Mark Dantonio’s squad looked anything but a Big Ten contender in Week 1, although the Spartans did have a bye last week to prepare for the Irish. With DeShone Kizer the clear-cut No. 1 quarterback in South Bend, that’s one less worry for Brian Kelly and Co. But what if Kizer was never shuffled in and out of the game against the Longhorns? The Irish will never know, but it was an error by Kelly that never should have been made. How costly will that mistake be by the end of the year?

Which USC team will show up in Palo Alto when the Trojans visit No. 7 Stanford? Clay Helton’s squad appeared to give up early in its blowout loss to Alabama, which was unquestionably a bad look. If Christian McCaffrey and the Cardinal jump out to a two-touchdown lead on Saturday, will ‘SC pack it in again? For all of the talk about a culture change under Helton, it is still unknown how much fight the Trojans will possess when facing adversity again.

Adversity is something that Oklahoma State has been dealing with all week following its home loss to Central Michigan on a play that never should have even occurred. But all is not lost for the Cowboys. While a defeat to the Chippewas certainly damages any CFP chances, what if the Pokes run the table—starting with a tough game this week at home against Pittsburgh—and win the Big 12? Would selection committee members essentially look at that slip-up against CMU with an asterisk in mind? It’s something to consider if Mike Gundy’s squad remains relevant in a Big 12 that has already had its contenders suffer early losses.

Perhaps the biggest mystery heading into this weekend, however, is what exactly will shake out at The Palace on the Prairie. No. 3 Ohio State heads to Norman to battle No. 14 Oklahoma, which looked anything but like the CFP participant it was last season in its season-opening 33-23 loss to Houston. A 59-17 home win over Louisiana-Monroe last week did not do much to alleviate concerns surrounding OU, which allowed Cougars quarterback Greg Ward Jr. to pass for 321 yards, failed to consistently protect quarterback Baker Mayfield and did not look like a well-coached football team in the opener. Perhaps the most head-scratching aspect of that game, though, was the lack of commitment to the ground game.

As gutsy and talented as Mayfield has proven to be in big games for OU, the offense under coordinator Lincoln Riley is at its best when the rushing attack is fully present. Against Houston, OU gained just 70 yards on 26 carries. The combination of Joe Mixon and Samaje Perine is arguably the best in the country, and the duo helped the Sooners rush for 288 yards on 46 attempts against ULM. But will that commitment to the ground be there this week against the Buckeyes? If it’s not, the Sooners won’t be long for the playoff race. As well as Mayfield will need to play for OU to come out on top, the Sooners’ star rushing duo needs to combine for at least 40 touches—carries and catches out of the backfield—for this offense to be balanced and operate at its peak. And the big boys up front need to play their best, too.

Offense isn’t the only concern in Norman, though. The OU coaching staff was understandably concerned about the number of big plays the team’s cornerbacks gave up against Houston. There were a few busted coverages in the third quarter against ULM, which is nowhere near as offensively gifted as the Buckeyes. If that happens against J.T. Barrett and Co., OU could be looking at a 1-2 start.

The opening five-day stretch of the college football season was exhilarating. Houston looked like a legitimate contender, Alabama once again played like the best team in the country and other major powers teased that they aren’t going away any time soon. But it was also a weekend of stumbles for some traditional programs. And those missteps have set up a long, arduous road on their prospective playoff journeys.

Saturday will serve as a key stopping point for a few teams, as we will see which ones make it another week as a CFP contender.

College football has always had the most meaningful regular season in sports, and some naysayers will argue that the playoff has taken some of the luster off of it. That’s a hard argument to make, however, when the stakes are so high on several campuses across the country this weekend.

And to think that we are only in Week 3.

MORE: 1-128 College Football Rankings – Week 3