Workmen carrying out renovations last week were shocked to find an old green medicine bottle labelled 'Asylum Wadsley' with the cork still in it tucked away under lead roof tiles above the nave.
It is believed the five inch long bottle came from a former psychiatric unit - latterly known as Middlewood Hospital and based in Wadsley that dates back to 1872 - but nobody has any idea how it ended up stuck high inside the city's cathedral roof.
Reverend Canon Keith Farrow said: "The workmen were quite shocked, you obviously would not expect to find that in a cathedral roof!
"It must belong to the former Middlewood Hospital. I suspect it could have been a workman who had been up fixing the roof decades ago and had put it there for safe keeping and forgotten about it. But we really don't know."
While there is no known link between the hospital and the cathedral, the bizarre tale took another unusual twist as it emerged Canon Farrow actually used to work at the mental health facility.
He said: "I worked there as a staff nurse from the late 80s to the mid 90s. The hospital closed in 1996 but we believe the bottle must date back decades.
"It is yet another curiosity we have discovered. It's the cathedral that keeps on giving."
Previous renovation work in 2013 discovered that 15 bodies had disappeared from the burial crypt of one of Sheffield’s most important families including three Earls of Shrewsbury.
Workmen discovered the historical mystery when they stumbled across the entrance to Shrewsbury tomb, where at least 17 members of the Shrewsbury family, who were the Lords of Sheffield Manor for generations, were laid to rest beneath the chapel cathedral.
However, only two coffins were inside, meaning 15 bodies were missing. Their whereabouts remain a mystery to this day.
Canon Farrow said he plans to put the most recent mysterious discovery on display in the cathedral's heritage corner.
He said: "It will be nice to put it on show with an old picture of the hospital. If anyone has any information about the bottle please come forward."
The cathedral's roof is being fixed using a £480, 000 grant from the First World War Centenary Cathedral Repairs Fund and is due to be finished by next March.
*Do you have any information about the bottle? Email [email protected] with the details.