Both players recently underwent surgery. Mayo needed a menisus repair in his left knee, and McKinney had fractured left foot that required surgery.
They become eligible to return after missing at least three games.
The Giants replaced Mayo and McKinney on the roster by signing tight end Eric Tomlinson and defensive back Brandon Williams. The team waived Tomlinson and Williams on Saturday.
Mayo is beginning his second season with the Giants. He played all 16 games, including starts in the last 13. He tied for second on the team with a career-best 80 tackles.
McKinney was the 36th overall selection this spring. He was competing for the starting safety spot opposite Jabrill Peppers when he was injured two weeks ago.