Sproles headed to the locker room early in the first quarter, and the Saints announced he was out for the rest of the game shortly before halftime.
It was unclear when the injury occurred, but Sproles had a 2-yard catch and was hit hard by Antonio Allen before leaving.
The versatile Sproles came into the game with 36 receptions, tying him with Kansas City's Jamaal Charles for the second-most among NFL running backs, four behind San Diego's Danny Woodhead.
New York also lost a key player on offense when wide receiver Jeremy Kerley was knocked out of the game with an elbow injury in the second quarter.
Kerley, the team's leading receiver, appeared to be hurt when he was on the ground after a running play. New Orleans' David Hawthorne hit Kerley's left arm, which rolled awkwardly under the linebacker's shoulder. Kerley immediately grabbed at his arm, was checked by trainers on the sideline and then headed to the locker room.
Jets safety Antonio Allen left in the third quarter with a possible head injury, and linebacker Garrett McIntyre was questionable to return with a knee injury.
AP NFL website: http://www.pro32.ap.org