In Week 2, a 35–27 loss to the Carolina Panthers, Sproles had 13 receptions for 128 yards. On November 2, 2012, Saints interim head coach Joe Vitt announced that Sproles would be out indefinitely due to a fractured hand. Sproles returned in Week 12 and played in the Saints' remaining games, finishing the season with 48 rushes for 244 yards and 1 touchdown, 75 catches for 667 yards and 7 touchdowns, 18 kickoff returns for 483 yards, and 23 punt returns for 183 yards.