Professional Music Technology is set to close if councillors approve plans for a restaurant that would see the music shop, which rents the site, move out.
Gaz Coombes, former lead singer of Oxford band Supergrass, said: “I’ve been going to PMT Music shop since I was young, as have many fellow musicians and friends.
“There is nothing like it in Oxford and it’s vital for the continual nurturing of Oxford music. If it goes, there will be a huge creative hole.
“It’s the cultural soul of Oxford and the birthplace of many great artists and musicians, with PMT providing an important hub for the vast amount of creative people living here.
“The idea of a Travelodge restaurant is ridiculous – a joke – and would simply set the Cowley Road back culturally and standardise a truly unique area of Oxford.”
More than 1,200 music fans have joined a Facebook group to save the Cowley Road store from closure.
Radiohead bassist Colin Greenwood and former Candyskins singer Nick Cope said the shop is crucial to the city’s music scene.
Mr Greenwood told the Oxford Mail he still bought all his equipment from the shop.
He said: “I love PMT. It is the first place I go to when I need to get anything. It is very down to earth. I have known those guys for a long time.
“It is a drop-in place to meet and chat. I still get my own gear and they can answer difficult technical questions about computers and synthesisers.
“My son, nine-year-old son Jesse, who is in a band, bought his first guitar there.”
Former Oxford band Candyskins frontman Nick Cope said: “I think it’s dreadful as I use it such a lot and I also recommend parents go there.”
Ronan Munro, editor of Oxford music magazine Nightshift, said “It’s vital we have a shop like that in Oxford, particularly on the Cowley Road as that’s historically where a lot of Oxford’s music scene came from.”
Travelodge says it will only open a 66-room hotel if it can have a restaurant on the ground floor.
A Travelodge spokesman said: “In opening this 66-bed hotel, we are making a significant investment into both Oxford and the Cowley Road area, and we expect to create up to 20 jobs. There is no branded budget hotel accommodation in the centre of Oxford and, thanks to its location, this hotel will be perfectly placed to offer the best value accommodation for visitors.”
The application will be heard by the west area planning committee tonight at 6.30pm.