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However the former Blackpool and Blackburn boss stopped short of ruling himself out if there was interest.
Appleton has become the favourite with several bookmakers in recent days to replace Gareth Southgate in the role.
"Speculation is speculation, but as far as I'm concerned there's nothing I'm aware of," he told BBC Radio Oxford.
Appleton confirmed he has not applied for the role, which Aidy Boothroyd has carried out on a caretaker basis since Southgate's promotion to senior team manager.
But the 41-year-old did admit the role is one that has obvious prestige and attraction.
"I think it would be hard for anyone to not want to manage an England side, and certainly one of the top two jobs in the country," he said.
"I would be a very stupid man to say I would never be interested in that."
Oxford United are currently 12th in League One, after Appleton guided them to automatic promotion from League Two last season.

Oxford United head coach Michael Appleton says no approach has been made by the FA for him to take over as England Under-21 manager.