Olga Fedori has already filmed her final scenes as Frieda, whose exit episode airs in May.
Frieda first appeared on Holby City in February 2010 and quickly became known for her no-nonsense attitude and straight-talking ways.
A BBC spokesperson told Digital Spy: "Olga has been a fantastic asset to Holby City and will be sorely missed by the cast and crew. Everyone wishes her all the best for the future."
They added: "Ever since Frieda achieved outstanding F2 results, she has been in hot demand but has chosen to remain loyal to Holby City.
"However, Frieda is not only well qualified but also very strong-minded, and viewers will discover which path she chooses next month."
Fedori's portrayal of Frieda secured her a shortlist nomination for 'Best Newcomer' at the National Television Awards in 2011.
> Read our January 2011 interview with Holby City's Olga Fedori
> Read more Holby City spoilers and news