Tosh was the nickname for Det Sgt Alison McIntosh, who worked with Det Insp Jimmy Perez (Henshall) to solve crime in Shetland.
After Henshall’s departure from the series, Tosh was promoted to DI and joined by Ugly Betty star Ashley Jensen as Det Insp Ruth Calder.
O’Donnell said she wanted to explore other acting opportunities.
“I grew up in this job,” she said.
“It has shaped me as an actor, and as a collaborator. It’s in my bones and in my heart. As are the isles themselves, which have become like a second home to me, and to my family.
“It’s not going to be easy to leave it all behind, but I am excited for the future, for new adventures, and to take everything I have learned and loved in Shetland forward with me, to whatever may come next.”
Paying tribute to the audience, cast and writers, she added: “Playing Tosh has been the greatest gift an actor could hope for.”