The San Francisco 49ers selected Mays in the second round (49th overall) of the 2010 NFL Draft. Mays was the fifth safety drafted in 2010, behind Eric Berry, Earl Thomas, Nate Allen, and T. J. Ward. In an interview with the "Sacramento Bee"′s Matt Barrows following the draft, Mays suggested that Seattle Seahawks head coach Pete Carroll led him to believe that the Seahawks would select him with the 14th overall pick, which they instead used to pick another safety, Texas' Earl Thomas. "I understand it's a business. But with it being a business, he needs to be honest. And that's all I was asking for", Mays said.