Piscotty's mother, 55, suffered from amyotrophic lateral sclerosis, better known as Lou Gehrig's disease, a neurological disorder. She was diagnosed with ALS in May 2017.
"The Athletics organization extends its deepest condolences to the Piscotty family on the loss of Gretchen," Billy Beane, the A's executive vice president of baseball operations, said Monday in a statement. "She was a devoted wife and mother, whose legacy will live on through her husband, Mike, and their sons Stephen, Austin and Nick."
Stephen Piscotty was with his mother and family at the time of her passing, according to manager Bob Melvin.
"Obviously as an organization and certainly the players, we have heavy hearts for him,'' Melvin said. "We know what he's been going through. He's been going through it for quite a while now. He's really close to his mom. We all feel bad about what he's been through and what he's going through right now.''
The A's planned to honor Gretchen by matching up to $50,000 in donations made to the ALS Therapy Development Institute via youcaring.com/piscotty.
Piscotty is expected to be placed on the bereavement list, Melvin said.
"From the moment we drafted and signed Stephen, he and his family became a part of the Cardinal family,'' St. Louis Cardinals president of baseball operations John Mozeliak said. "We were saddened to hear of the passing of Gretchen and want to let Stephen and his family know that we pass on our heartfelt condolences.''
Cardinals manager Mike Matheny coached Piscotty for three seasons in St. Louis and knew the family well.
"I remember them from the draft all the way through,'' Matheny said. "It's been a tough go for them, so I'm thinking about them and praying for their family. You just can't put a template on how to go through that and how he's supposed to handle it. Stephen is a first-class guy himself, and a great family. I'm just hurting for them all the way through.''
In December, the Cardinals traded Stephen Piscotty to the Athletics for two minor leaguers. The move meant Piscotty, who grew up in nearby Pleasanton, California, and went to Stanford, could aid in his mother's care. Piscotty described being close to his mother as "priceless" to the San Francisco Chronicle at the time of the trade.
"We usually end [the day] playing the guitar with 'Amazing Grace,'" Stephen Piscotty told ESPN about taking care of his mother. It was a song she used to play for him on a music box as a child. "It's definitely emotional. Playing it is kind of a full-circle aspect going on there. It gives me some little bit of peace, and I hope it does the same for her.
"It's important to spend time with her because we're running out of it, and we're just trying to cherish every moment."
Piscotty, 27, made his Cardinals debut in 2015 and finished sixth in National League Rookie of the Year voting after hitting .305 in 63 games. He missed some games last season to be with his mother.
In 2017, he signed a six-year, $33.5 million contract extension that runs through 2022.
"With or without the illness, I'm very grateful they're all close by," Gretchen Piscotty told the Chronicle in January, in reference to her sons. "I wish this wasn't impacting them, impacting the family, but I'm very grateful to see them. They're all very tender and caring and gentle with me."
The Associated Press contributed to this report.