Sharapova, who enjoyed a recent run to the French Open quarterfinals, has had an injury-plagued start to the season and cited the need for rest as the reason for her withdrawal. Keys will miss the Wimbledon tune-up due to an abdominal injury.
"I have good memories of Birmingham," the two-time Edgbaston champion Sharapova said. "So I'm disappointed not to be able to play this year. I need to take care of my body and make sure I stay healthy and sometimes that means you have to take tough decisions like this one. I wish everyone in Birmingham a great tournament."
Keys, an American who reached the semifinals at Roland Garros, added: "I am sorry to have to pull out of Birmingham this year. Everyone knows how much I love playing on grass and I was looking forward to starting my grass season there, but unfortunately I aggravated an injury I sustained in Rome and need to rest as much as I can right now. I look forward to returning to Birmingham next year and playing in front of its great fans."
Croatia's Donna Vekic has been added to the lineup, which features current Wimbledon champion Garbine Muguruza and two-time SW19 titlist Petra Kvitova. British No. 1 Johanna Konta will also feature at the event, which begins June 18 at the Edgbaston Priory Club.