Simulation Picks
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Expert Picks
The Colts get their starting center back from injury, not to mention exciting rookie RB Marlon Mack, and Peyton Manning will be inducted into the team's Ring of Honor on Sunday. There's value here because of what happened to Indy in the second half Sunday night on national TV. Back the Colts to send San Fran to 0-5.
Both teams really struggle in pass defense. Look for the offensive units to have their share of downfield success and generate enough points to send this one Over the total.
The 49ers have looked competent at time and have a great defensive front in the making, but come on. They should be getting three points on the road against anyone, particularly for a 1 p.m. ET start time that has proven tricky for even experienced West Coast teams to navigate. A Colts defense that hung around in Seattle for a half and getting healthier should be able to handle a 49ers offense that is still trying to find its feet despite scoring 39 against the Rams in Week 3.