The New Orleans Saints selected Colston in the seventh round (252nd overall) of the 2006 NFL Draft. Colston was the 32nd wide receiver drafted in 2006.
On July 14, 2006, the New Orleans Saints signed Colston to a three-year, $1.10 million contract that includes a signing bonus of $24,600.
He made his professional regular season debut in the New Orleans Saints' season-opener at the Cleveland Browns and made four receptions for 49-yards and scored his first career touchdown. He made his first career touchdown reception on a 12-yard pass by quarterback Drew Brees during the third quarter. On October 29, 2006, Colston caught six passes for 163 receiving yards and had a season-high two touchdown receptions during a 35-22 loss against the Baltimore Ravens in Week 8. The following week, Colston made a season-high 11 receptions for 123 receiving yards and one touchdown during the Saints' 31-14 victory at the Tampa Bay Buccaneers in Week 9. In Week 10, Colston recorded 10 catches for a season-high 169 receiving yards during a 38-31 loss at the Pittsburgh Steelers. His performance marked his third consecutive game with over a hundred receiving yards. Colston sprained his left ankle during a Week 11 31-16 loss to the Cincinnati Bengals and missed the next two games. Colston finished his rookie season with 70 receptions, 1,038 receiving yards, and eight touchdowns in 14 games and 12 starts.