Leading 17-10 at halftime, the Ragin' Cajuns' Kris Moncrief returned an interception 67 yards for a touchdown in the third quarter and Kenneth Almendares added a 28-yard field goal in the fourth.
The Colonels (0-2) rallied with a pair of touchdowns in the final five minutes, but the second came with only 33 seconds remaining and Nicholls failed to recover an onside kick.
Lewis was 19-of-33 passing with completions to 11 ULL (1-1) receivers. Michael Jefferson led with 84 yards and a touchdown. John Stephens also caught a scoring pass.
Lindsey Scott was 26 of 37 for 359 yards passing with three touchdowns and the pick-6. Scott added 121 yards rushing on 18 carries. Dai-Jean Dixon made a school-record 14 catches and tied another school mark with 198 yards receiving while going over 3,000 career yards. He caught two TD passes.
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