Parking will be suspended on Ecclesall Road from 18:30 on Saturday to 16:00 on Sunday, and on Fulwood Lane, John Street, Ringinglow Road, Rushley Road, Woodhead Road, Norfolk Street and Surrey Street for much of the weekend.
Road closures include:
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A61 Ring Road from 08:30 to 13:30
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Arundel Gate from 04:00 to 16:00
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Charter Row from 08:30 to 13:45
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Ecclesall Road from 08:00 to 13:30
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Hathersage Road from 09:00 to 12:45
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Knowle Lane from 09:00 to 13:15
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Moore Street from 08:30 to 13:45
Sheffield Mutual is sponsoring the event for the second year running.
Chief executive officer Jamie Bellamy said he was looking forward to taking on the challenge himself.
He said: “As a local organisation, we believe in supporting events that bring people together and make a real difference to the community.
“The half marathon is a fantastic celebration of determination and camaraderie, and I’m especially looking forward to taking on the challenge myself.”
The event will raise money for a number of charities, including Sheffield Children’s Hospital, Weston Park Cancer Charity and the Lauren Currie Twilight Foundation.
Last year the race was won by Samuel Moakes with a time of 1:08:58 and Abbie Pearse with 1:12:18.
A full list of road closures is available here, external.