Hilda Braid, who plays Nana, will film her final scenes later this year for a heartbreaking Christmas storyline.
Jessie Wallace (Kat Moon) and Shane Richie (Alfie Moon) are also leaving the soap in December.
An insider explained, "Everyone loves Nana, but with Shane and Jessie going and Christopher Parker gone, she won't have any family left. It's sad, but all good things must end."
Another source added, "Nana gets very sick."