Michael Douglas' marriage "went downhill" immediately after his HPV admission.
The 68-year-old actor claimed his throat cancer might have derived from contracting the sexually transmitted disease through giving oral sex.
And his wife Catherine Zeta-Jones was reportedly enraged when she heard his comments.
"It all went downhill from there," a source told British newspaper The Sun.
Speculation is rife their union is on the rocks largely due to their mutual health issues.
Zeta-Jones suffers from bipolar disorder and most recently exited a rehab facility for depression in May. And Douglas fought a long battle with throat cancer since revealing he had the tumorous disease in 2010.
Supposedly the media circus and "stress has taken a toll on their relationship" and the couple have lost touch with each other entirely.
"We have not seen much of Michael here with Catherine for about 18 months," a local near the spouses' Bedford, Connecticut mansion shared with the publication.
"Most of his friends are in New York. He likes the city and she likes horses and playing golf. They're like chalk and cheese."
A media representative for the couple confirmed now that they are "taking some time apart to evaluate and work on their marriage".
Zeta-Jones and Douglas married in November 2000, and the brunette previously revealed she found divorces "repulsive" and insisted it was "in her genes" to remain married for life.
The estranged couple share two young children together, Dylan, 13, and Carys, 10, and they will ensure their youngsters are well cared for whether or not they decide to divorce.
"They want the best for their kids, no matter what happens," a source told People magazine.
E! Online reports Douglas is preparing to attend the Deauville American Film Festival this weekend, his first event since publicly announcing his separation.
He and Zeta-Jones were first introduced at the Deauville Film Fest in 1998.
- Cover Media