Sam's death comes just three months after his wife of 28 years Kelly Preston lost her battle with breast cancer.
The news of Kelly's tragic passing was broken by PEOPLE via a statement from a family representative, who revealed she chose to keep her fight with breast cancer private.
John shared an image of his late wife on Instagram confirming Kelly's death shortly afterwards.
"It is with a very heavy heart that I inform you that my beautiful wife Kelly has lost her two-year battle with breast cancer," he wrote in July.
"She fought a courageous fight with the love and support of so many. My family and I will forever be grateful to her doctors and nurses at MD Anderson Cancer Center, all the medical centers that have helped, as well as her many friends and loved ones who have been by her side."
He went on to say: "Kelly’s love and life will always be remembered. I will be taking some time to be there for my children who have lost their mother, so forgive me in advance if you don’t hear from us for a while. But please know that I will feel your outpouring of love in the weeks and months ahead as we heal. All my love, JT."
John recently shared an Instagram post in honour of what would've been Kelly's 58th birthday.
The Grease actor shared two images - one of his and Kelly's 1991 wedding and another of John's parents on their own big day.
"Happy Birthday hon!" John captioned the post.
"I found this photo of my mom and dad‘s wedding. It was nice to see ours alongside theirs. All my love, John."
John and his late wife share daughter Ella, 20, and nine-year-old son Benjamin.
In 2009, the family lost their 16-year-old son Jett following an epileptic fit while the family were on holiday in the Bahamas.
"Certainly having little Ben has been a beautiful kind of glue for us to re-bond after tremendous loss," John said in a 2016 interview with Good Morning America.