The series, which has followed the highs and lows of the staff and patients on the wards of the fictional Holby City Hospital since 1999, will broadcast its final episode next March.
Taking to Twitter, one upset viewer said: "WAIT WHAT???!!!! No more #HolbyCity!!!!! I literally grew up with this show and it's coming to an END! You better give it the send-off that it deserves!"
WATCH: Are you a fan of Holby City?
Another added: "I genuinely can't believe this. All that history, the sets, the cast and the crew. Im utterly gutted. I just hope Casualty won't succumb to the same fate any time soon."
A third wrote: "That's terrible news. What a shame for all involved. Thanks for the last 23 years and we'll definitely miss you every Tuesday night."
In a statement released on Wednesday, the BBC called the move to cancel the series a “difficult decision”, but said it would make room for new shows that would "better reflect, represent and serve all parts of the country".
The BBC series has been airing since 1999
The statement from the broadcaster reads: "We are incredibly proud of Holby City but it's with great sadness that we are announcing that after 23 years, the show will end on screen in March of next year.
"We sometimes have to make difficult decisions to make room for new opportunities and as part of the BBC's commitment to make more programmes across the UK, we have taken the difficult decision to bring the show to a close in order to reshape the BBC's drama slate to better reflect, represent and serve all parts of the country. We would like to take this opportunity to thank the amazing team at BBC Studios and all the cast and crew who have been involved in the show since 1999.
"Holby has been a stalwart with audiences, delighting millions of viewers each week and winning hundreds of awards with a compelling mix of cutting edge medical stories and explosive personal stories.
"We look forward to working with the team over the coming months to ensure that when it ends, Holby goes out on a high."
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