Nicks fractured the fifth metatarsal of his right foot while running a route during individual drills in the team's practice facility. He will have surgery Friday and the approximate expected recovery time for the injury is 12 weeks.
The procedure will be performed by foot and ankle specialist Dr. Robert Anderson in Charlotte, N.C.
Nicks is coming off a career season for the defending Super Bowl champions, catching 76 passes for 1,192 yards and seven touchdowns.
It's the second major injury the Giants have suffered in two days of OTAs. On Wednesday, cornerback Brian Witherspoon reinjured his ACL and was carted off the field. Witherspoon was waived Thursday and the team signed defensive back Dante Hughes to replace him.
In 2010, Nicks missed the last four games of the season with a broken toe in his left foot.
The fifth metatarsal generally takes a long time to heal because there isn't a lot of blood flow to the area.
Brooklyn Nets center Brook Lopez was limited to five games this past NBA season after breaking his fifth metatarsal in training camp. He returned after missing 33 games of the league's shortened season, and then sprained an ankle on the same foot and never came back.
Cornerback Prince Amukamara, the Giants' first-round draft pick in 2011, broke his fifth metatarsal in training camp on Aug. 6. He did not play in a game until Nov. 20 and he never looked 100 percent in his rookie season as the Giants won a Super Bowl.
The Giants will have a total of nine OTAs before mandatory minicamp June 12-14. They report to training camp at the University at Albany on July 26.
Information from ESPNNewYork.com's Jane McManus and The Associated Press was used in this report.