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The venue, where First Minister Nicola Sturgeon received both her AstraZeneca jabs, is being handed back in preparation for the Cop26 UN climate change conference later this year.
The SSE Hydro will host its final day of vaccinations on Sunday.
NHS Greater Glasgow and Clyde (NHSGGC) said it will now be moving fully on to the next stage of the vaccination programme, which will focus more on mobile facilities and drop-ins at community settings, alongside planned second dose appointments.
The vaccination centre moved to the SSE Hydro in April following the closure of NHS Louisa Jordan, the temporary hospital at Glasgow’s Scottish Exhibition Centre (SEC).
Jane Grant, NHSGGC’s chief executive, said: “Our vaccination rollout has been a great success so far and as we now move into the next stage of the programme and look ahead to potential Covid-19 vaccine booster requirements, it is important we can continue to provide an accessible and flexible service to members of the public.
“This is why our focus is now very much on community drop-ins and the use of mobile vaccination facilities which allow us to continue to connect with communities as well as make provision for people who may not be able to attend a scheduled appointment due to work or family commitments.
“It is so important that everyone who is eligible has the opportunity to be vaccinated and I would encourage anyone who may not have come forward yet, but would now like to, to drop-in to the Hydro on Sunday.
“We look forward to welcoming anyone aged 18 years old and over for their first dose, as well as people who had their first vaccination at least eight weeks ago and would like their second."
She thanked all staff who have worked at the SEC campus and everyone who has come forward for their vaccination.
NHSGGC said almost 3,000 vaccinators have worked at the Hydro, while more than 800 support staff and hundreds more council workers and volunteers have also been involved in what has been the “largest mass vaccination programme undertaken”.
The health board has administered approximately 1.4 million vaccinations, and more than 555,000 people have received both doses.
Health Secretary Humza Yousaf said: “By close of play on Sunday every adult in the NHSGGC area who attended their scheduled appointment will have received their first dose, but we urge anyone who hasn’t come forward for whatever reason to pop into the Hydro as staff mark its final day as a vaccination centre.
“Staff there have made a massive contribution to the successful rollout of the vaccination programme, carrying out up to 5,000 vaccinations a day, and I want thank each and every one of them.
“It is now time for the site to be handed over in preparation for Cop26, as was always the intention.
“The transition from the Hydro will be seamless with no negative impact on vaccination capacity and appointments have been allocated to alternative clinics, although of course, people can always head along to one of the many drop-in clinics now operating in the area if they prefer.”