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Colorado's difficult schedule continues Saturday afternoon when the Buffaloes host No. 8 USC, which is their third ranked opponent already this season. They opened the season with an upset win over then-No. 17 TCU, but they are coming off a 42-6 blowout loss at then-No. 10 Oregon. USC has won all four of its games by double digits, including a 42-28 win at Arizona State last week. The Trojans cruised to a 55-17 victory when these teams met in Los Angeles last November.

Kickoff is set for noon ET at Folsom Field in Boulder. The latest USC vs. Colorado odds via SportsLine consensus list the Trojans as 22.5-point favorites, which is down two points from the opener (-24.5), with the over/under at 73. Before making any Colorado vs. USC picks or bets, be sure to check out the college football predictions and betting advice from SportsLine football expert Jimmie Kaylor

Kaylor is a NFL, college football and DFS expert for SportsLine, who has covered the NFL and college football for close to a decade as a member of the Pro Football Writers of America. His background as a former college football All-American and NFL player gives him a unique perspective when building his fantasy lineups and locking in his betting picks. As a Colorado native, he has his finger on the pulse of the local and national sports scene and has been cashing big on Denver area teams for the last two years. 

Kaylor has been red-hot on his football picks this season for SportsLine, posting a 9-2 record thus far. He has been especially strong on his Colorado picks this season, going 6-2 on his best bets in the Buffs' first four games of the season. Anyone who has followed his picks is way up.

Now, he has set his sights on Colorado vs. USC and just locked in its picks and CFB predictions. You can head to SportsLine now to see Kaylor's picks. Here are several college football odds and betting lines for USC vs. Colorado:

  • Colorado vs. USC spread: USC -22.5
  • Colorado vs. USC over/under: 73 points
  • Colorado vs. USC money line: USC -1628, Colorado +883
  • CU: QB Shedeur Sanders is averaging 352.5 passing yards per game.
  • USC: The Trojans are averaging 569.3 yards of total offense per game.
  • Colorado vs. USC picks: See picks at SportsLine
  • Colorado vs. USC live stream: fubo (try for free)

Why Colorado can cover

In his short time in Boulder, Coach Prime has proven to be a masterful motivator. With the spotlight and millions of eyes on this game, it's safe to expect the Buffs to come out swinging. After being thoroughly dominated by Oregon, the Buffs will be facing a USC defense that has allowed 20 points and 364.5 total yards per game to opponents with substantially less offensive talent than what CU has.

Junior quarterback Shedeur Sanders was under constant pressure and got sacked seven times against Oregon. USC will likely attempt to bring a steady dose of pressure, but this time around Sanders and the Colorado offense will be playing within the friendly confines of Folsom Field. Sanders enters this matchup with 1,410 passing yards, 11 touchdowns and one interception. See which team to pick at SportsLine

Why USC can cover

Colorado's struggles against conference opponents continued last week, as the Buffaloes are winless in their last seven games against Pac-12 teams, covering the spread just once during that stretch. They were in a 35-0 hole by halftime of their game against Oregon, as quarterback Shedeur Sanders finished with just 159 passing yards. Sanders cannot afford another poor outing on Saturday, as USC's offense leads the country in scoring at 55 points per game.

Defending Heisman Trophy winner Caleb Williams has completed 74.3% of his passes for 1,200 yards, 15 touchdowns and zero interceptions. Williams was only intercepted five times in 500 pass attempts last year, so he continues to excel at taking care of the ball. USC has won all 16 meetings between these teams all-time, and the Trojans have too much firepower for Colorado to handle on Saturday. See which team to back at SportsLine

How to make USC vs. Colorado picks

Kaylor has analyzed this matchup from every angle and he's leaning Over on the point total. He has also discovered a critical X-factor that has him jumping all over one side of the spread. He's only sharing what it is, and which side to back, at SportsLine.

Who wins Colorado vs. USC in the Pac-12 Conference home opener for Deion Sanders, and which critical X-factor makes one side of the spread a must-back? Visit SportsLine now to see Colorado vs. USC picks, all from the expert who has covered college football for over a decade and is 6-2 on his Colorado best bets in 2023, and find out.