But because of a "recent deterioration" in her health and the "advanced nature" of her illness the decision was made for her to be put down.
Moti was born at Helsinki Zoo in Finland in 1994 before moving to Bristol in 1996 where she has lived ever since.
She had her first cub in 1998 but it only survived for a few days.
She went on to give birth to two more cubs, Indi and Dacca, later that year and a third, Aiesha, in 2001.
The trio have moved on to other zoos as part of the managed conservation breeding programme.
The zoo says it will now contact the programme to seek another lioness as a mate for Kamal, their male lion.
Asiatic lions are a critically endangered species with just 300 left in the wild.
They live on a small reserve in the Gir Forest in western India - an area smaller than the New Forest